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BioMed Research International
Volume 2013 (2013), Article ID 102819, 11 pages
Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors
1Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China
2Department of Nuclear Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325003, China
3Zhejiang University Medical PET Center, Zhejiang University, Hangzhou, Zhejiang 310009, China
4Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, Zhejiang 310009, China
5Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang 310009, China
6Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Received 17 July 2013; Accepted 8 August 2013
Academic Editor: Mei Tian
Copyright © 2013 Ling Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.
1. Introduction
Neuroendocrine tumors (NETs) are unique tumors that originate almost everywhere in the body from neuroendocrine cells [1]. They have secretory granules which can produce biogenic amines and polypeptide hormones [2]. All these tumors share the features of the neuroendocrine cell system [3]. NETs have particular characteristics including low incidence, low proliferation rate, and sometimes the hyper secretion of biologically active substances [4]. The diagnosis of lesion is limited because it has slow metabolic rate, small size, and various localization [5]. Those NETs of unknown primary may have a relatively favorable prognosis [6]. The primary sites in gastrointestinal and bronchopulmonary tracts are most frequent [7]. Gastroenteropancreatic neuroendocrine (GEP-NET) tumors are neoplasms with variable clinical expressions. They produce and secret various amines and peptides, which can be used as tissue and circulating markers [8], representing approximately 2% of all gastrointestinal tumors [9]. Pheochromocytomas are malignant in approximately 10% of patients. The histology of benign and malignant tumors has no obvious differentiation. The malignant tumors are diagnosed by the presence of metastatic lesions or recurrence [10].
Overall, 5- and 10-year survival rates of NETs were 78 and 63%, respectively [11]. There are various clinical behaviors of NETs. They may have a function or not. The clinical use of specific radiolabeled ligands for imaging and therapy is based on the presence of peptide receptors and transporters at the cell membrane and the neuroamine uptake mechanisms of NETs. Because the majority of NETs express somatostatin receptors (SSTR) which bind to somatostatin (SST), they can be successfully targeted [2]. The understanding and diagnosis of NETs have been greatly improved by morphologic and functional imaging modalities [12]. This paper is a systematic review about the somatostatin receptor-based molecular imaging and therapy for NETs.
2. SST and SSTR
SST is produced by neuroendocrine, immune, and inflammatory cells in response to many kinds of factors, such as ions, nutrients, neuropeptides, neurotransmitters, and thyroid [13]. It is present in the cerebral cortex, the brain stem, the hypothalamus, the pancreas, and the gastrointestinal tract. It is a cyclic and regulatory peptide consisting of 14 amino acids [13, 14]. A family of G-protein-coupled receptors mediates the function of SST which comprises five distinct subtypes (characterized SSTR1-5) [13, 15]. The SSTR subtypes overexpressed in NETs are related to the type, origin, and grade of differentiation of tumor [16]. A number of different tumors have receptors for SST [17]. SSTR expresses in various regions such as the brain, the adrenals, the pancreas, and the gastrointestinal tract [18]. SSTR also distributes in tumor tissues of neuroendocrine origin. SSTR is overexpressed in various human cancers. The overexpression of SSTR is a characteristic of NETs, which can be used to localize the primary tumor and its metastases by imaging with the radiolabeled SST analogues [19]. Receptor targeting with subtype-specific radiolabeled SST analogues is based on the structural differences between SSTR subtypes. The imaging of the SST subtype 2 (SST2) overexpressing NETs has been developed and has had extensive clinical applications for almost two decades [20].
There is significant variation in SSTR subtype expression between the tumors of the same type [21]. The majority of tumors expressed SSTR types 1, 2, 3, and 5, and a minority expressed SSTR4 [22]. The expression of SSTR2 on pancreatic endocrine or carcinoid tumors is predominant [21]. The clinical use of SST is limited because it has a short half-life (about 2 minutes) in plasma [23]. SST analogues used to evaluate the use and effectiveness of the management in NETs patients have been synthesized widely. The radioisotopes used in nuclear medicine both for imaging and therapy are showed in Table 1. Imaging with SST analogues is considered as imaging method of first choice for NETs because it has high specificity, low antigenicity, rapid clearance, and good tissue penetration [24]. Octreotide and octreotate are widely used as SST analogues, and the role of SST analogues in the clinical use is well established. This review summarizes the clinical use of SSTR imaging and therapy in NETs as well as the use of SSTR as a platform for gene report imaging.
3. The Clinical Use of Radioisotope Labeled SSTR in NETs
3.1. Somatostatin Receptor Imaging (SRI)
SRI is widely used for the diagnosis, as well as staging and restaging of NETs [25]. NETs are usually diagnosed by a combination of clinical symptoms, histology, and hormonal excess. After diagnosis of NET is established, a search for its localization is carried out using common morphologic imaging methods in the past [26]. However, it is difficult to use conventional imaging techniques to map the lesions accurately. There is an urgent need to establish better imaging modalities to detect the lesions for NETs. The tracers used for SPECT and PET in NETs are showed in Table 2.
3.2. Single Photon Emission Computed Tomography (SPECT) Imaging
111In-pentetreotide used to be the first choice for the visualization of receptor for SST analogues. Tumors and metastases that express the SSTR subtypes SSTR2, SSTR3, or SSTR5 can also be visualized in vivo after injection of 111In-pentetreotide [27]. It differentiates scar tissue from tumor recurrence after the pituitary surgery or radiotherapy. Another agent, [111In-DTPA(0)]octreotide (111In-DTPAOC), is also a tracer of a great potential use for the imaging of SSTR-positive tumors. 111In-DTPAOC scintigraphy is also a scintigraphy modality of choice for NETs. Still, there are patients in whom imaging findings are negative or weak positive [28]. 111In-DOTATOC is reported to be of great value for the diagnosis of patients with octreotide receptor-positive tumors [29]. The efficacy of scanning with 123I-octreotide was evaluated by localizing tumors in 42 patients with NETs. It was found that those often unrecognized primary tumors or metastases were visualized in 12 of 13 patients with carcinoid tumors as well as in 7 of 9 patients with endocrine pancreatic tumors.
There is an overall high sensitivity of SRI to localize NETs. The value of SRI in patients with NETs has been proven [17, 30, 31]. The scintigraphy provides important information in NET patients and has a strong impact on further therapeutic management [31]. Both positive and negative results of SRI are very useful; the former may predict the effect of octreotide therapy to NETs [17].
3.3. Positron Emission Tomography (PET) Imaging
68Ga-labeled somatostatin analogues are widely used [2]. The two compounds frequently used in functional PET imaging are 68Ga-DOTA (0), Tyr (3) octreotate (68Ga-DOTATATE) and 68Ga-DOTATOC [32]. 68Ga-DOTATATE PET/CT is a useful imaging modality for NETs. In 38 patients, the sensitivity is 82% [33]. Another study of 18 patients with pulmonary NETs showed that all typical carcinoids showed a high uptake of 68Ga-DOTATATE [34]. The comparison of the 111In-DTPAOC SPECT and 68Ga-DOTATOC PET shows that the latter is superior in detecting small lesions with low tracer uptake [35]. In another comparison study of 84 patients with known or suspected NETs, 68Ga-DOTATOC PET shows a significantly higher detection rate compared with SPECT and diagnostic CT [36]. A study of 40 patients with metastatic NETs who underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT reported that the two had almost the same accuracy for the diagnosis of NET lesions; however, standard uptake value (SUV) max of 68Ga-DOTATOC scans is higher than 68Ga-DOTATATE (Figure 1) [32]. It was also reported that the diagnostic value of PET/CT with 68Ga-DOTATATE and 68Ga-DOTATOC in the same patients with GEP-NET is almost the same, but the maximal uptake of 68Ga-DOTATATE tended to be higher than 68Ga-DOTATATE [37].
A case reported that, in a patient who had synchronous colorectal cancer and pancreatic NET, the 68Ga-DOTATATE PET and 18F-FDG PET imaging showed two different tumor types within the liver metastases. This case suggested that combinational 68Ga-DOTATATE PET and 18F-FDG PET imaging modalities are of potential use in understanding the biology of the NETs and managing the NETs [38].
Several novel agents have been developed. DOTANOC is the first compound for PET imaging and is reported to have a higher affinity for SSTR2 as well as for SSTR5 [39]. The first in-humans study with 64Cu-DOTATATE imaging had an excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111In-DTPA-octreotide. It identified additional lesions in 6 of 14 patients (43%) [40]. 18F-fluoropropionyl-Lys0-Tyr3-octreotate (18F-FP-Gluc-TOCA), another new carbohydrate analog of octreotide, is under research [41]. In 25 patients with different SSTR-positive tumors, 18F-FP-Gluc-TOCA showed a fast and intense tumor accumulation and a rapid clearance from blood serum [42].
A study concluded the sensitivity and specificity of SSTR PET or PET/CT in detecting thoracic and/or GEP-NETs, which were 93% and 91%, respectively [43]. PET resulted in a modified restage in 12 patients (28.6%), while the treatment plans were affected in 32 patients (76.2%). It prevented unnecessary surgery in six patients, while two patients with lesions that did not express SSTR were excluded from PRRT [44]. 68Ga-DOTANOC PET/CT can affect the tumor staging and modify the treatment in more than half the patients [19]. To predict the therapy response earlier in tumors is essential to guide the therapy and at the same time avoid the side effects and lower the costs caused by ineffective therapies [45]. However, using conventional imaging techniques and response criteria to assess treatment response is often complicated [12]. Decreased 68Ga-DOTATATE uptake in lesions after the first cycle of PRRT correlated with clinical symptoms improvement and predicted time to progression in well-differentiated NET patients [45].
3.4. Somatostatin Receptor Targeted Radionuclide Therapy (SRTRT)
The treatment of the NETs includes peptide receptor therapy, somatostatin analogues, and surgery [28]. Surgery is still the therapy of first choice, while the vast majority of NETs will need further treatment with SST analogues and/or interferon [46]. There are few treatment options for those metastasized or inoperable endocrine GEP tumors. Chemotherapy for those NETs may be effective, but the response usually lasts less than one year [47]. The predominant expression of SST2 receptors in NETs is essential for the application of radiolabeled octapeptide SST analogues [21], as well as for PRRT using 90Y- and 177Lu-DOTATATE/DOTATOC [48]. The radiological response was measured with response evaluation criteria in solid tumors (RECIST) criteria [49]. SSTR PET imaging, including the common tracer 68Ga-DOTATOC, is becoming the basis of the selection of candidates for PRRT [50]. Patients with high 68Ga-DOTATOC uptake (SUV > 5.0) were recommended to 90Y-DOTATOC therapy [51, 52]. For those NETs that demonstrate uptake in scintigraphy with 111In-octreotide, the therapy with 111In/90Y-octreotide is a modality [46].
90Y-DOTATOC is a potential choice which can deliver high absorbed doses to tumors expressing SST2 receptors, and the therapeutic response is achieved in about 25% of patients [23]. High-dose 90Y-DOTATOC targeted radiotherapy is a well-tolerated treatment which has significant clinical benefit and objective response for NETs [53]. A phase 2 study included 38 patients with advanced stage well-differentiated NETs treated with a fixed 90Y-DOTATOC dose of 2.56 GBq bimonthly showed that 43.6% patients had a partial response (PR), 25.6% had stable disease (SD), and 28.2% had progressive disease (PD) and that the median progression-free survival (PFS) was 22.3 months. The treatment of metastatic NETs with fixed activity is reported useful and safe [54].
Antitumor effects of 90Y-DOTATOC have been reported considerably different between various studies [55]. A review revealed that the objective response rates are in the range from 20% to 28% for all NETs with 90Y-DOTATOC therapy. In patients with GEP-NET, the response rate was in the range from 28% to 38%. Overall, the cumulative response rate was 24% [56]. The objective responses were 5 PR, 7 minor responses, 29 SD, and 17 PD in a phase I dose-escalating treated study of 90Y-DOTATOC in 58 patients with SSTR-positive GEP-NET. Furthermore, there is a significantly longer overall survival (OS) compared with historic controls [57]. In metastatic NET patients, the result was complete response (CR) 4%, PR 23%, SD 62% in 116 patients, and PD 11%, and 90Y-DOTATOC also induced a better outcome [58]. Sowa-Staszczak et al. reported that 90Y-DOTATATE therapy results in symptomatic relief and tumor mass reduction in NETs. The response was 47% SD, 31% PR, and 9% PD, and the PFS was 37.4 months [59]. Clinical PR at six months was in 43 of 60 (72%) patients with histologically proven GEP-NETs after 90Y-DOTATATE treatment, and 9 patients had SD, and PD was noted in 8 patients. PFS was 17 months, and the OS was 22 months [49].
177Lu-DOTATATE, another radiopharmaceutical for treatment purpose, was used in GEP-NET patients. It was reported that CR and PR occurred in 2% and 28% of patients, respectively, and minor tumor response occurred in 16%. There was a 40 to 72 months survival benefit from diagnosis when compared with historical controls [60]. Treatment results with 177Lu-octreotate are preferable in patients with a limited lesion. Even in patients with no PD, early treatment may be better [47]. In the same patients, same dosage (3,700 MBq) of 177Lu-DOTATOC and 177Lu-DOTATATE was administered in different stages of treatment to see which should be preferred for PRRT. It indicated that the 177Lu-DOTATATE residence time of tumor was longer than 177Lu-DOTATOC [61]. This therapy is available, safe, and effective and has no serious adverse events [62]. 177Lu-DOTATATE is efficacious on small lesions when compared with 90Y-DOTATOC, which seems to be more efficient in bigger lesions [23, 63]; however, fractionated therapy with 177Lu-DOTATATE should be considered as a treatment option also for those patients with large tumors, high proliferation, and high receptor expression [64]. Studies with 177Lu-DOTATATE indicate that more cycles of such therapy are still safe. The median PFS is longer than 40 months [65]. The quality of life of those patients was improved remarkably after the therapy. Kwekkeboom et al. advocated 177Lu-octreotate therapy in patients with GEP tumors not waiting for tumor progression because of the high success rate and the absence of serious side effects (Figure 2) [66].
With 177Lu-DOTATATE treatments, tumor regression of 50% or more was achieved in 28% of patients. In 19% of patients, tumor regression was in 25% to 50%, SD showed in 35%, and PD showed in 18% of patients [55]. Quality of life is improved remarkably after treatment with 177Lu-DOTATATE [55, 67]. The combination of 177Lu-octreotate and capecitabine treatment was safe and feasible and may enhance these antitumor effects [68]. The study including 50 patients with metastasized NETs which compared combined 90Y/177Lu-DOTATATE therapy with single 90Y-DOTATATE showed that tandem radioisotopes therapy gives longer OS than a single one [69].
Oh et al. evaluated the effect of PRRT on the glucose metabolism and SSTR density assessed by 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT, respectively. Only 56% (77/138) of the lesions show matched SSTR expression and glucose metabolism; the relationship is complicated [48]. In another study, the number of tumor lesions identified on 177Lu-DOTATATE scans during PRRT for dosage purpose was compared to those detected on 68Ga-DOTATATE studies obtained before the therapy; 318 lesions were detected in a total of 44 patients, while 280 (88%) lesions were concordant. Among those discordant lesions, 29 were 68Ga-DOTATATE positive and 177Lu-DOTATATE negative, whereas 9 were 68Ga-DOTATATE negative and 177Lu-DOTATATE positive. The sensitivity, accuracy, and positive predictive value for 177Lu-DOTA-TATE were 91%, 88%, and 97%, respectively, as compared to 68Ga-DOTATATE [70].
Radiolabeled octreotide analogues therapy is effective in patients with NETs [71], especially for GEP tumors [63]. The repeated cycles of PRRT enabled stabilization of the disease and did not cause an obvious toxicity increase of PRRT. Radiolabeled receptor-binding SST analogues (octreotide and lanreotide) target radioactivity to tissues expressing SSTRs which can be used for the management of NETs [63]. Side effects are described, and information on SST analog treatment is provided [72]. It is suggested that the octreotate PRRT is better when compared to octreotide in reducing diarrhea and flushing [61]. We summarize the studies that evaluate the PRRT efficacy in NETs in Table 3.
Dose-limiting factors for PRRT are kidney and/or bone marrow dose [61]. The uptake of 68Ga-DOTATOC was low in almost all organs except the kidneys [73]. The amount of radioactivity that can be used safely depends on the radiation dose to the kidneys [71]. The range of particles from 90Y is maximally 12 mm, which is long enough to reach the glomeruli; however, the range of the 177Lu electrons is shorter, maximally 2.1 mm, which causes much lower average decline in creatinine clearance in the latter patients than in the former patients [71]. The dose-limiting toxicity of 90Y-DOTATOC is renal insufficiency, starting at dose of 7.4 GBq/m2 [74]. However, the kidney and blood morphology parameters changes were transient [75]. When kidney protective agents are used, the side effects are few and mild [76]. PRRT therapy might become the first-line therapy in patients with disseminated or inoperable GEP-NETs [55]. The predictive factors for tumor remission include high tumor uptake on SRI and limited amount of liver metastases.
4. Somatostatin Receptor Based Reporter Gene Imaging
The human SSTR subtype 2 (hSSTr2), as a reporter gene, is under research for molecular imaging applications which have several features for potential translation to human studies [73, 77]. In vitro and in vivo studies have been done for this reporter system [73]. There are two approved SST analogues used for the expression of the reporter gene imaging [77]. SSTR2 is used as a reporter probe for imaging of gene transfer in animal models [78]. A study showed that the hSSTr2 cell membrane expression was proportional to the in vivo uptake of this radioligand demonstrated in tumor-bearing mice by small-animal PET of 68Ga-DOTATOC [73]. It is also verified by 111In-pentetreotide imaging that the ex vivo SST2 gene expression in tumor samples was positively related to the in vivo semiquantitative determination of SST2 protein [79]. 1, an SST analog, was internalized rapidly into AdHASSTR2-infected A-427 cells, which will improve the sensitivity of the SSTR2 reporter gene system [78]. Briganti et al. studied nine neuroblastoma tumors with 111In-pentetreotide SPECT for SST2 and found that the ratio between the radioactivity in pathological and background area was increasing between early and late acquisitions. Moreover, the rate of this pathological increase was significantly related to the expression of SST2 gene [80].
The imaging of gene expression is critical to monitor gene transfer. There are great benefits for gene therapy trials from the use of noninvasive imaging to determine the location and time course of gene transfer [78]. Reporter transgenes with low endogenous expression levels are useful for this purpose [81]. 111In-octreotide detected the SSTR2 portion of the fusion protein in vivo (biodistribution studies and gamma-camera imaging) and in vitro (receptor-binding assay). This method can be used to monitor the delivery of a gene of interest directly and noninvasively [82]. Cotugno et al. used adeno-associated viral (AAV) vector-mediated gene transfer to murine muscle and liver which has low hSSTR2 expression and 68Ga-DOTATATE PET. They found that the levels of tracer accumulation correlated with the dosages of AAV vector used [81].
A study used a tumor model with an adenoviral vector encoding the human type 2 SSTR (Ad5-CMVhSSTr2) and a radiolabeled somatostatin-avid peptide (P829) to evaluate the level and location of the expression of the transferred gene [83]. Gene transfer technology can improve the degree and specificity of radiolabeled peptide localization in tumors [84]. The hSSTr2 was monitored as a reporter gene for (an SST analogue) imaging showed adenoviral gene transfer to cancers, such as ovarian cancer [85]. This is a noninvasive imaging method for imaging gene transfer to ovarian cancer, which is helpful for planning a human gene therapy trial.
5. Discussion
Significant advances have been made in the imaging of NETs, but the challenge is to find the ideal imaging method with increased sensitivity and better tomographic localization of the primary and metastatic disease [86]. SRS is an ideal modality for evaluating NETs patients, which is not affected by their proliferative activity. Furthermore, when those patients have negative results on SRS, FDG PET should be used [87]. Both SPECT and PET can be very helpful in diagnosing NETs; however, PET may give more accurate information about the primary and metastatic lesions of NETs. PET or PET/CT is recommended as a first-line diagnostic imaging technology in patients with suspicious NETs [43]. The in vitro affinity of 68Ga-DOTATATE binding with the SST2 is higher than that of 68Ga-DOTATOC. However, the uptake value of the latter is higher than the former. The 68Ga-DOTATATE uptake and the histologic grade of NETs were not correlated [28]. Functional imaging with both 68Ga-DOTATATE and 18F-FDG is of potential use for a more comprehensive tumor assessment in intermediate-grade and high-grade tumors [33]. 68Ga-DOTATOC uptake in the head of the pancreas is commonly found in patients undergoing 68Ga-DOTATOC PET/CT. Therefore, quantification should be used to avoid false-positive diagnosis [88]. Furthermore, neither 111In-DTPAOC SPECT nor 68Ga-DOTATOC PET imaging was sensitive in the detection of liver metastases since they showed a lower uptake than the surrounding normal liver tissue compared to CT [35]. Recently, a new 11C-5-HTP-PET has been reported that is sensitive in small NET lesions imaging and can image more tumor lesions than SRI and CT [89]. Moreover, scintigraphy of the upper abdomen is affected by breathing artifacts, so misalignment due to respiratory motions must be considered [88].
Despite the fact that most GEP-NETs are slow growing, OS in NET patients with liver metastases is 2 to 4 years. In metastatic cases, there are limits of cytoreductive therapeutic options [60]. PRRT is a promising new method in the treatment of patients with inoperable or metastasized NETs because of its fewer side effects and less toxicity and better curative effect [86]. Individual dosimetry seems helpful for deciding whether a patient can be chosen for radiolabeled DOTATOC or DOTATATE therapy or not and deciding the therapeutic modality for each patient [32]. Evaluation of NETs therapy response is difficult; for assessing such response, the monitoring of functional parameters is more accurate than morphologic measurements [45]. A positive scintigram suggests good response to treatment with octreotide in many cases [19]. The foundation of the dose-response relationship and the decision of the correct dose of PRRT are important to achieve an ideal treatment [56].
Beta particles with higher energies and longer range emitted by 90Y may be preferable for larger tumors, while 177Lu that emits beta particles with shorter range and longer half-life may be a good choice for small tumors. In patients with tumors of nonhomogeneous receptor distribution and various sizes, a combination of radionuclide might be useful [69]. 90Y-DOTATOC therapy has proven to be an effective and safe treatment. Before and after the therapy, blood tests for kidney, liver function, and chromogranin A were performed. During 12 months followup, transient decrease of PLT, WBC, and hemoglobin values and GFR values were found [59]. The mild critical organ toxicity does not limit the PRRT of NETs [59]. Standard dosages of 90Y-DOTATATE result in a relatively low risk of myelotoxicity. However, because of risk of renal toxicity, the kidneys shoud be monitored carefully [49]. The further goal is to further reduce renal toxicity so that higher doses can be administered [53].
68Ga-DOTATOC is a specific ligand for hSSTr2 reporter system and so that for hSSTr2 reporter gene PET imaging. Because DOTATOC has been tested clinically, this reporter system can be used for translation to human studies [73]. The relative level of gene expression for SST2 was positively related to patient outcome in the childhood neuroblastoma tumor and neuroblastoma tumor. Imaging with 111In-pentetreotide may have not only a diagnostic but also a prognostic value [80]. There is great use of peptides for imaging gene transfer with the hSSTr2 reporter receptor, specifically when the reporter correlates with the expression of therapeutic genes [83]. Selective internal radiation therapy (SIRT) is a well tolerated and effective treatment for nonresectable NET with liver metastases [90].
6. Perspective
The SSTR-based molecular imaging is a noninvasive and quantitative method to diagnose the NETs and evaluate the therapeutic efficacy for NETs. The development of radiolabeled SST analogues has affected the clinical management of patients with NETs. PET/CT can be useful in the early prediction of the treatment outcome of NET patients who underwent PRRT. Furthermore, the clinical management of NETs will be further improved if better radioligands are developed and more technologies are used to identify the radiotherapy treatment response in patients with NETs.
Dual therapy is a promising method to treat NETs. The combination of PRRT and EBRT can increase the dose delivered to the tumor and reduce the dose for organs at risk. The clinical use of molecular imaging is not only in diagnosis and treatment efficacy evaluation, but also in patient selection. Still, it plays an important role in the reporter gene research. Personalized diagnosis and treatment of NETs will be established based on increased understanding of molecular mechanisms of NETs.
NETs: | Neuroendocrine tumors |
GEP: | Gastroenteropancrea |
SSTR: | Somatostatin receptors |
SST: | Somatostatin |
SST2: | Sst subtype 2 |
SRI: | Somatostatin receptor imaging |
SPECT: | Single photon emission computed tomography |
111In-DTPAOC: | [111In-DTPA(0)]octreotide |
PET: | Positron emission tomography |
68Ga-DOTATATE: | 68Ga-DOTA(0), Tyr(3)octreotate |
SRS: | Somatostatin receptor scintigraphy |
CT: | Computed tomography |
PRRT: | Peptide receptor radionuclide therapy |
SUV: | Standard uptake value |
18F-FP-Gluc-TOCA: | 18F-fluoropropionyl-Lys0-Tyr3-octreotate |
SRTRT: | Somatostatin receptor targeted radionuclide therapy |
RECIST: | Response evaluation criteria in solid tumors |
PR: | Partial response |
SD: | Stable disease |
PD: | Progressive disease |
PFS: | Progression-free survival |
OS: | Overall survival |
CR: | Complete response |
hSSTr2: | Human somatostatin receptor subtype 2 |
AAV: | Adeno-associated viral |
SIRT: | Selective internal radiation therapy. |
Conflict of Interests
The authors declare that they have no conflict of interests.
This work is partly sponsored by Grants from the Zhejiang Provincial Natural Science Foundation of China (Z2110230), Health Bureau of Zhejiang Province (2011ZDA013), and National Science Foundation of China (NSFC) (no. 30672396). This work was reprinted by permission of SNMMI from Poeppel et al. [32].
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I just started my beading renaissance this winter. Normally I go to my cabin in the woods and bead, but my mom is 90 and I am primary caregiver, and now she doesn't want to be left alone. Consequently, it could take me weeks to do a piece of beadwork at the cabin. This winter, I loaded up my beading supplies and brought them to the house, where I have been beading daily.Recently, my favourite event is going to bead stores. I love seeing what new things have come in, and getting more beads for my stash. As they say, too much is not enough!I like to work on bracelets because they are a shorter project that lets me try out new ideas - like my current free-form peyote ones. I'd also like to try some bead embroidery.I have so much to learn and become skilled with! I like BD's free E-Books that you can download. The projects are a great way to learn a new technique. I buy beading magazines and learn from their published projects. I use folders to organise articles and how-to's I have gleaned off the internet. I like to look at beadwork from Etsy. Sometimes I despair when I see gorgeous pieces. I feel I'll never learn that level of skill and artistry. My biggest challenge is coming up with original designs. I want to be able to go to craft shows with my own pieces, as I respect copyrights.What else? I'm updating my camera equipment so I can take some decent photos of my work, then I can have a blog (I love reading other people's beading blogs!).My inspirations come mostly from colours and forms and textures found in nature and spiritual things. Well, to me, nature is spiritual. I live in a forest where there is lots of inspiration. You know you're a beading addict when you look at something and think "How can I translate that into beads?" My current piece that I'm working on is a cluster of beaded marsh-marigold flowers. I hope I will be able to post some photos when I am done.Cheers everyone, Teresa
Hi Teresa - I certainly understand where you're at. I have a 50 hour a wk job plus a part time job, and in off time I'm also care giver of an elderly parent with health issues. Hard to make time for beading sometimes. Heck, hard to make time for washing dishes sometimes! But I have a wonderful Uncle who takes my dad out quite often. God Bless him. Dad doesn't want to see an ironing board or hear the vacuum. So you go like a demon when my uncle comes for him. Makes it tough to follow a muse, right? Oh, he also doesn't like my beading. Bad daughter that I am, I tell him I get to have time for me, too. I look forward to Sunday afternoons the most!
Like you, I often wonder "How can I do that on a cuff?" Or make something into a pendant or focal. Also like you, I make what I can find patterns for, as it teaches me much. Eventually that just takes off into something else entirely, all on it's own. As though there is no control over it. Those turn out to be my favorite pieces.
There's a current challenge going on right now, for wedding jewelry. Obviously, you need to design your own (not my strongest yet). It has certainly pushed me beyond my comfort zone, and I think I may have hit my head against the wall more then I should have. But it's fun. Perhaps when someone throws the next one out, you could also join in?
Regardless, I look forward to seeing your work
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Tue, Aug 9, 11 at 23:40
In Home Depot recently, I saw some disposable towels, like a thick paper towel. I think they were made by Brawny.
I thought these would be great for polishing my counters ( I don't like that waxy stuff on my regular towels), staining furniture, etc. Just wondered if anyone used them and are they much thicker/better than a paper towel? Thanks |
Follow-Up Postings:
Haven't use them, but I want to make a pitch for buying the $1 bag of rags sold at Goodwill. They are off white cloths, nice size, and cheap enough to use for throw away projects like staining furniture. |
My sister and I don't bother buying shop rags. We use old bath towels, you know, the worn ones with rips, stains, holes. We keep them in the basement for using to clean up water and other liquid spills, cleaning, etc. She calls hers dog towels and I call mine shop towels. I do buy paper towels for use in the kitchen. |
No, I use garage sale bath towels, flannel sheets, baby blankets, etc.. |
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Program Components
Course/Pedagogy Redesign
This component is faculty-driven and will focus on modifying pedagogy and content delivery to improve Hispanic student success, university academic quality, management, and fiscal stability. Course redesign efforts will build on university strengths and use models that have been proven effective in national and university research. Faculty will be have the opportunity to be trained in several models of course redesign, all of which integrate, active learning, student-centered learning, student support, or increase community-based learning opportunities. Specifically, models from the National Center for Academic Transformation (NCAT), Collegiate Learning Assessment (CLA), and ETS Criterion will be used.
Strengthening Efforts to Make Hispanic Students Success: A Fresno State and Community Priority
This component aims to develop and strengthen Student Affairs partnerships and other related offices to extend an array of student services and make more explicit links between academics and student services on campus. This component will also develop stronger partnerships between the university and the community it serves. Hispanic students will be actively encouraged to renew and deepen their commitment to academics by engaging in a variety of proven out of classroom activities such as community-based service learning and community-based research in the Central Valley.
At the completion of the HSI – Title V grant, we hope that best practices from our efforts will be institutionalized to improve the academic achievement and success for all students at California State University, Fresno.


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Jyothi Bhatt
Jyothi Bhatt is an Ayurvedic specialist, yoga therapist, and massage therapist. She completed a five-and-a-half year Ayurvedic medical course in India, after which she received a bachelor's degree in Ayurvedic medicine and surgery. At her college's Ayurvedic specialty hospital, Jyothi managed numerous cases with panchakarma, botanical medicine, and diet and lifestyle counseling. She weaves all of these modalities together in her clinical practice and educational workshops. www.svastha.us
Upcoming Programs
Dates | Program |
February 13–22, 2015 | Ayurvedic Health Counselor, Module 2: Etiology, Pathology, Clinical Assessment, and Pulse Analysis |


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Public Policy Polling just released their survey on the Kentucky races, and it looks like David Williams is no longer just trying to lose by less than Ernie Fletcher. He's in Peppy Martin territory.
Here's the bloody carnage:
Steve Beshear — 55 percent
David Williams — 28 percent
Gatewood Galbraith — 10 percent
Yes, that number you see at the front of Williams' percent is a "two." Considering Williams has gone from being down 21, to down 24, to down 27 in the last three polls, we can't really be certain that he'll beat Peppy Martin's 22 percent from 1999 when she was the Republican gubernatorial nominee.
(Oh, and 21 percent have a favorable view of Williams, compared to 57 percent negative. Carnage.)
In races down the ballot, things are surprisingly close, with only Democrats Jack Conway and Todd Hollenbach with comfortable leads. Here they are:
Jack Conway — 47 percent
Todd P'Pool ('pee pool') — 36 percent
Adam Edelen — 34
John Kemper — 31
Alison Lundergan Grimes — 38
Bill Johnson — 35
Bob Farmer — 36
James Comer — 37
Todd Hollenbach — 43
KC Crosbie — 28
Ken Moellman — 16
These races appear to be all about name ID right now, which is why Jack Conway has the highest percentage and the rest are fairly even. While Conway is up, the fact that almost everyone knows him and he's not above 50 percent against a complete unknown has to be a little bit unnerving, though.
Edelen and Grimes are in tighter races than expected, but they'll be on the air nonstop in the final month against broke candidates, so their situation is probably safer that it appears in this poll.
Farmer vs. Comer? Y'all might want to flip your coin on this one.
And Ken Moellman polling 16 percent is a) bizarre, b) a sign that there's a libertarian tea party fringe that doesn't like the Republican Party one bit, and c) Todd Hollenbach is somehow going to serve eight years in a statewide constitutional office.
Odds on whether the RGA/King Coal/Crossroads GPS/Koch Brothers even bother putting up ads for Williams, or just throw in the towel? Actually, they might just cut ads for P'Pool now (seriously).
In the meantime, Peppy Martin is going to be really excited over the next two months, you can be sure of that.


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I bought a variegated gardenia late last summer at Green Thumb. It has survived the winter very well, but I'm afraid that if I leave it in the pot (3 gallon) it will die. I need to get it in the ground, but I'm afraid I am going to kill it. The one that I bought from you has yellow leaves right now and I'm afraid it may die.
Anyway, I want to root the variegated one so that if I do kill my 'mother' plant, I will still have some. Can I take cuttings now? How big does the cutting need to be? Assuming that I actually get the cutting to root in water, when should I put it in a pot with potting soil? My plant from you has some new leaves, but they are a chartruse yellow. I've added liquid soil acidifier and liquid iron and sulfur pellets. My pH is very high, so I think that is the problem. My soil also doesn't drain very well, so that probably doesn't help either. Hence my concern for my other plant. Hope everything goes your way tomorrow!
Follow-Up Postings:
- Posted by tsmith2579 Z7B/8A-Alabama (My Page) on Mon, Mar 13, 06 at 13:30
Well, I'm not Rosemary but I just potted up 16 rooted cuttings last Saturday so I do have some experience. I always wait until after the gardenias bloom. That seems to be the right time to prune, also the right time to take cuttings. I take 8 inch tip cuttings, remove the mature leaves, stick the stems in some Rootone, stick them down in a pot of sandy-loam, keep them damp and place them in light shade. I took 18 cuttings last July 4th weekend and 16 survived. I left them outdoors all winter in sheltered spot. Last summer, they sat under shade of the banana trees. Just keep them watered. - Terry |
- Posted by roseyp8255 z8 - SC AL (My Page) on Mon, Mar 13, 06 at 21:25
Hey Rae, and thanks Terry. I take cuttings sporadically - dip some in rotting hormone and some not - put them in shot glasses in the windowsill and change the water on a weekly basis. I usually pull all but the top 2 leaves off - and somehow, i have miraculous luck! :) My gardenias are yellow leaved right now too - gotta fertilize this weekend. Now, that being said - i have been known to amend the soil tremendously when i plant - the extent of a couple of feet out from the rootball.... Deposition rescheduled by Butthead's attorney until next Friday - naturally. |
- Posted by anaturelover z7AL (My Page) on Mon, Mar 13, 06 at 21:55
Rae, you are in zone 8 so you don't need to worry. I was given a rooted gardenia which of course outgrew it's pot in one year. I planted it outside close to the south side of the house and it is now about 7 ft tall. I live in zone 7(Huntsville) so it should live at your place easily. The easiest way of rooting them is to bend over a branch in late spring and cover with earth or sand. I have rooted 2-3 to give away. Let them stay at least a year and they will grow into a nice little plant which you then sever from the mother plant with a shovel and a good scoop of earth and move them. Yellow leaves is sometime a signal of not enough acid in soil. They like an Azalea type of fertilizer. Good luck. |
Thanks everyone, I 'll give it a try! Rosemary, I'm sorry you were postponed. I know you will be very relieved once everything is finally over. Hang in there. Rae |
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Good to see the ladies doing the mandatory promo
for their upcoming reunion album, with their brand new
winter issue cover of Annex Man Magazine.
But, it raises the question; should they be reuniting in a climate
where girl groups have proven unsuccessful, and both Pop & R&B
girl groups are still struggling to capture a spot on very
volatile, single driven, music chart listings?
Regardless, cheers to them for going for it.
As for the question; record sales may ultimately be
the only true indication of the answer, so we'll see.
But they look good. Good luck ladies. – Troy Monaco


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Soul Shift
Soul Shift is a fabulous physics puzzle game that you will enjoy playing. The main objective in the game is to remove the red shapes from the playing field. By swapping the positions of the shapes to trigger actions that will cause the red ones to fall off the screen. As the levels increase, more removable and explosive items come into play making the tasks even more challenging. Avoid swapping too many times because by doing so you will lose the chance of earning stars. Strive to get all the three stars in each of the 30 exciting levels of the game. If you have enough stars, you can even play in the five bonus levels of the game.
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text: | Dáil Éireann - Volume 400 - 27 June, 1990 Written Answers. - Central Bank Report. Mr. Bell Mr. Bell 83. Mr. Bell asked the Minister for Finance his views on the recent Central Bank report regarding pay policy, low inflation and the Programme for National Recovery. Minister for Finance (Mr. A. Reynolds) Albert Reynolds 1062 Minister for Finance (Mr. A. Reynolds): I presume the Deputy refers to the annual report of the Central Bank, [1062] published in May. I fully concur with the Central Bank's views on the importance of competitiveness. Improved competitiveness is a vital catalyst for increased growth and employment. This is evident from the growth and employment performance during the Programme for National Recovery. The annual growth rate of GNP over the life of the programme is expected to be 3½ per cent, and non-agricultural employment is expected to increase by 16,000 on average this year, following on an increase of 13,000 in 1989. We can aspire to continue on this path of progress only if we remain competitive, especially in the challenging context of closer European integration. Pay moderation, in particular, is essential if the virtuous circle of improved competitiveness and increased growth, referred to in the Central Bank report, is to be sustained. Realism in pay settlements has been a feature of the Programme for National Recovery and must be central in any follow-on arrangement. As the record of the programme shows, pay moderation can be fully compatible with improvement in workers' living standards.The combination of moderate pay increases, low inflation, and the taxation relief which has been possible in the past two years and into 1990, means that the real take-home pay of workers with average industrial earnings will have increased by 4 per cent to 8½ per cent over the three years of the programme. This compares with a fall in purchasing power of 7 per cent to 11 per cent over the period 1980 to 1987, when money incomes grew far more rapidly. 1063 Inflation is on a downward trend since November of last year. The benefits of our strong exchange rate, and the reductions in VAT and excise duties which I announced in the budget, were in evidence in the Consumer Price Index for Mid-May. This showed a year-on-year increase of 3.5 per cent compared with an increase of 4.2 per cent for mid-February.The inflation rate should decline further in the remainder of the year. It is expected that the year-on-year increase in prices will have fallen to around 2½ per cent by year-end. As I [1063] stated in my budget speech, there must be unrelenting action to control inflation and costs of all kinds. My views on this are consistent with those expressed in the Central Bank report. Dáil Éireann 400 Written Answers. Central Bank Report. Questions 19900627 | ||||||||||||||||||||||


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| Email | Full Article (TrendHunter.com/id/147027) |
Rami Niemi digitally renders minimalist recounts of pop culture exchanges. His use of primary colors and thick bold lines is reminiscent of 70s illustrations, such as the Little Miss characters. Niemi's work is highly simplistic, betting on an edge of perfectionism and mathematical involvement. The works are often bulbous, playing on a round motif, which nicely juxtaposes with the sharp satirical edge of the incorporated message. With titles such as "Splurgeth sporadically on VG 90s Vinyl," and "Unleasheth your inner Justin Vernon," these pieces are definitely spunky and memorable.
Rami Niemi has often been described as a hipster. His site even reads, " He will certainly brew you a cup and treat you to a danish — if he doesn't happen to be in the nearby record shop hunting for some hopelessly knackered Proto-grunge LP." However, his harshly satirical images seem to be making more of a mockery of hipster culture than praising it. The images may be minimal, but remain highly dynamic.


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In 2004, the Congress decided that "Constitution Day" should be observed in schools each year on September 17th with educational programs about the history and signing of the Constitution. To help celebrate Constitution Day, eight newspapers and the New Hampshire Supreme Court have sponsored an annual "Constitution Day Essay Contest" for grades 5-12 on a topic related to our constitutional rights as citizens. Winning essays are published in the participating newspapers and winners are invited, along with parents and teachers, to a special reception at the state Supreme Court and to the Nackey S. Loeb School of Communications First Amendment Awards.
Be prepared Now for "Constitution Day" on September 17, 2014
A statewide effort to promote informed citizenship
and start a dialogue about the Constitution
2014 Constitution Day material
- The topic and backup material
- The rules
- Entry form
- Constitution Day letterhead
- The timeline, for your reference
- A couple of suggestions for your letters
In the suggestions for teachers' letters, I have included word of the rule changes involving the length of essays and the number of local winners each paper may chose.
David Tirrell-Wysocki
Executive Director
Nackey S. Loeb School of Communications
627-0005 (school)
340-3619 (cell)
Acrobat Reader format. You can download a free reader from Adobe.
Microsoft Word format. You can download a free reader from Microsoft.


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Full disclosure: the day that DJ Snake shit truly went down, Carnage hit me on the DAD phone like "I got some ish for you." After him saying Breaux was a legend, it made sense. I just wasn't truly ready for it. And while many of you hate the drama that permeates the EDM scene, it's hilarious to see how many of you flock to the drama. In any case, Carnage's "Mara" got the full-on festival trap look via this Carnage x Breaux VIP, and if your life is all about turning up, turn the fuck up. No word on when you can own this one, but don't worry; YouTube won't die anytime soon.
as soon as… soundcloud stops being gay.. im uploading #MARAVIP w/ @breauxxmusic for freeeee download <3
— CARNAGE (@djcarnage) January 11, 2014


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Welcome to CMV Truck & Bus
CMV Truck & Bus represents one of the world's great automotive franchises, the Volvo Group. The brands the Volvo Group market in Australia are Mack Trucks, UD Trucks, Volvo Trucks and Volvo Buses.
CMV Truck & Bus has been associated with the Volvo Group for many years, and now has a total of six dealerships and 20 satellite operations throughout Australia. We service a customer base that provides a wide range of transport services to our country's population.
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We pride ourselves on going the extra distance for our customers to ensure that CMV Truck & Bus, the manufacturer and the customer work together to ensure maximum productivity from the vehicle.


text: By control on May 31, 2012 tagged Air Cargo World Magazine, Asia, World News Garuda Indonesia appears to be developing an appetite for cargo. In a fairly short period, the Indonesian carrier's ambitions have advanced from a desire to augment belly-hold revenue to a plan for full freighter flights to take off before 2013. In early April, Garuda CEO Emirsyah Satar announced his decision to... Login | register to read more and post comments More Latest Magazine Related Articles Oman Air sees record FedEx sees sluggish numbers, packs up freighters Ruslan International tames the AN-124-100 Where have all the freighters gone? The integrators are coming!


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Fresh ideas on nature and community.tagged: Ethanol
March 05, 2013 · By Cassandra Profita
Why We're So Far Behind On Biofuel Targets
A major cellulosic ethanol project is underway in Boardman, but the U.S. is hopelessly behind on reaching its targets for production nationwide.
Continue reading →Filed under: Renewable energy, Ethanol, Biofuel
Jan. 09, 2013 · By Cassandra Profita
Troubled Oregon Ethanol Plant Now Shipping Oil
Filed under: Energy, Columbia Pacific Biorefinery, Ethanol
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Sat, Mar 24, 12 at 15:37
I have recently been looking at the eco4 and Nora housing combo. Just saw that Nora now offers a Cree based led solution,their diamond series. The Nora led runs triple the cost of the eco4. Anyone have an idea what you get with the Nora diamond led vs the eco4 other than a larger bill? |
Follow-Up Postings:
From reading the specifications, 1. More trim options 2. Higher output 613 lumens vs 575 lumens. The actual light output per watt through is lower (55.75 vs 60.5) The Cree CR4 has the advantage of having a significantly larger distribution channel and production run. Technical info |
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Tuscaloosa, Ala: Michael Antonio Long, 20, was arrested Thursday for allegedly robbing a pizza delivery driver who came to deliver two pies, Newser reported. Long ordered the pizza by phone and had it delivered to his home in a mobile home park in Tuscaloosa, Ala.
When the driver arrived, Long and several other men allegedly armed with handguns robbed the man of all the money he had on him, his wallet and the two pizzas he was carrying, AL.com reported. The driver got a good look at the suspects and described them to police. Investigators talked with people in the trailer park who mentioned that one man fitting the description of one of the robbers lived in the mobile home where the pizza was delivered. That man was later identified as Long.
An officer who knocked on Long's door found the stolen pizzas and the delivery bag, the Tuscaloosa Times reported. The officers appreciated the convenience. "We don't typically see a suspect call a delivery driver to their actual address to commit a robbery," Sgt. Brent Blankley told the paper.
Long was charged with first-degree robbery and remained in the Tuscaloosa County Jail on Friday with bail set at $60,000.
fucking nigger needs the death sentence cuz he will do it again and again and again etc.
If I had a son, he would look like Michael. He is simply redistributing the wealth of the more fortunate of our society, those squares who work for a living.
Is that Shareeka?
Actually, there are areas north of Baltimore where food is no longer delivered, for just this reason. The cops always catch the would-be thieves because the idiots practically lead them to the door. There's a reason people call that stuff "dope".
Oh, what a treat! here we see the North American Pavement Ape in it's predatory stance! shhhh, let us watch how the Great Ape not only procures food for himself and his many children but also tools!
Oh what a treat! what a beautiful animal, the North American Pavement Ape!
It's nigga's like that who give blacks a bad name. Get off your fucking ass and work for a living. Rot in hell.
Yalls a bunch of racist crakkkers up in here.
it be 2014 and you crakkkers still racist
We taxpayers are still going to be supporting him to the tune of 30-40 grand a year in the big house. But on the plus side he won't be reproducing and making future gangbangers- at least for a few years.
When will this race learn? God I hate using the N word but come on! I am still waiting for them to prove they can work hard, and not rob, kill, and beat each other on a regular basis. The "We is held down by other races" is pure B.S. btw.
Shit for brains.
As a white American man, I am always suspected of being racist. My reply is "how can I be racist? I haven't gotten through hating all the stupid fucking white people yet." The comments here prove my point.
@ Earnest. How is what these people say raciest? It's the truth. Please show me uplifting articles about black? Show me the low crime stats of black on black crime? P.s. How do you know I am not a black female? You assume much.
Ironically , the only post here that proves your point " earnest " is your own.
There is a LOT of whites on this site and y'all sitting back waiting and waiting to pounce as soon as the next black shows up to put up your third grade racist B.S. Even going as far as to pose as a black woman to try to get a rise out of folks(shareeka). Too bad the only place you can be brave and witty is online; I would like to see you step to a real black man and spout that trash.
typical nigger talking crap…. I'd like to see a black stand up to a white without being in an ape pack of 3 or more…
also neverscared your people are always scared, that's how they earned the name spooks.
Neveracared dey do be a lot of crakker racsist in hear and dey do be just pickin on da few black people DAT get posted dats why I hate Dem nasty stank ass crakkkas dey all racsists
I see where you call me a wite ans I ain't yous jus a house nigger ackin wite
I don't care about this guy's race. He is probably a career criminal who WANTED to go back to jail. 3 squares a day, cable tv, internet, medical and dental care, never have to work a day in his life, no job skills or education. Jail is his best option. Career criminals should be put down like a rabid dog. They will never be productive members of society, and are a danger to those who are.
I do the same thing but a bit different. I call in an order and hide. If the delivery driver is a female I jump out naked and piss all ova dat bitch! If its a dude i give them a quick blast in the eye and run. My stream is pretty potent and has been known to cause temporary blindness.
@troof be told
I read that to the voice of Steve Irwin.
hilarious. lol.
Still having fun on this on I see…I guess racists/trolls need an outlet to be keyboard commandos having fun with impunity; I have my fun too: I see this all the time– a white person shoots up a joint, the discussion is about the person themselves, or gun control, politics, mental health, yada yada. Black man screws up, the ENTIRE race has to be dissected. But that's always been the case. Y'all must really hate that you couldn't find ONE qualified White dude to keep a Harvard educated brother from being the most powerful man on the planet, TWICE. Going out buying up guns and ammo, trying to move to Canada and everything. I didn't get mad when Bush 43 got two terms, just chill. Feel free to reply….peace.
do you go to the anti white websites and tell them the same crap you are spewing here? no, no you don't little nigger boy.
yes we know it isn't all niggers that are bad, sorry for the 99% of the niggers making the 1% of the good ones look bad.
also nigger obama got in because he lied, cheated and bullied his way in. and nigger obama is going down in history as the worst president in history.
I promise some white people aren't like this….
I know it's hard to believe.
and some are nigger lovers… make excuses and bend over backwards to make their ape people seem somewhat human.
Oh sam, throw that N word around some more. You really make the white race look good doing that. The only stupid thing I'm seeing here is the stupid white guy calling talking like a Klannie. Me as a white guy have seen enough stupid white people as it is. So from one white person to another, you're one dumb honky, cracker.
Needs alot of Butter.
He has no job skills, a problem with authority figures. He will never have a job in his life. he is a career criminal. Save the American taxpayers several hundred thousands of dollars. Kill him now.
60,000 ouch…Now he will have to rob at least 6000 more delivery drivers to pay that off…
Why am I not surprised he is from the same scum ball city as that horrible university of Alabama. I bet he plays on that terrible satan ran football team, that's why im not surprised such a mindless action took place.
Jesus Christ, there are a lot of racist fuckfaces on this site.
Hell Yeah! We about to get paid my Nigga! This crime is a verse straight out of The Dead Prezidents song Hell Yeah! Pay attention to what rap teaches the dumbass, broke, it ain't my fault, somebody gots to feed these kids, niggers.
Can't he just loot, riot, and cause mayhem like a normal brutha?
© Copyright 2012 Mugshot Row |


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text:
The Global Intelligence Files,
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On Monday February 27th, 2012, WikiLeaks began publishing The Global Intelligence Files, over five million e-mails from the Texas headquartered "global intelligence" company Stratfor. The e-mails date between July 2004 and late December 2011. They reveal the inner workings of a company that fronts as an intelligence publisher, but provides confidential intelligence services to large corporations, such as Bhopal's Dow Chemical Co., Lockheed Martin, Northrop Grumman, Raytheon and government agencies, including the US Department of Homeland Security, the US Marines and the US Defence Intelligence Agency. The emails show Stratfor's web of informers, pay-off structure, payment laundering techniques and psychological methods.
[OS] Corrected: FLOTUS POOL Report #1
Released on 2012-10-16 17:00 GMT
Email-ID | 4930649 |
Date | 2011-10-01 02:17:22 |
From | email@example.com |
To | email@example.com |
List-Name | firstname.lastname@example.com |
From: Lennon [mailto:firstname.lastname@example.com]
Sent: Friday, September 30, 2011 6:59 PM
To: Schake, Kristina
Cc: Kinder, Charmion
Subject: Fwd: POOL Report #2
Revised version.
From: firstname.lastname@example.com
Date: September 30, 2011 6:45:40 PM EDT
To: "Lennon" <firstname.lastname@example.com>
Subject: Re: POOL Report
PORTLAND - First lady Michelle Obama told hundreds of supporters today
at a Portland fundraiser that the presidential election will determine
the nation's future for generations.
The election presents a stark contrast between two visions and a GOP
victory will hurt working families, she said.
"Whether it's health care or the economy or education or foreign policy,
the choice we make in this election will determine nothing less than who
we are as a country and who we want to be," she said.
The 25-minute speech focused primarily on her husband's policy
initiatives, and some of those initiatives require patience, she said.
"Change that is lasting and meaningful takes time," she said.
About 650 people paid at least $100 each to attend today's rally, which
featured appearances by the state's top Democrats, U.S. Reps. Chellie
Pingree and Mike Michaud. Donors in the "preferred" section paid $250.
Pingree told the crowd the she met Obama earlier in the day and found
herself "star struck."
"She's tall, outspoken and smart," Pingree told the crowd. "I can't say
how pleased I am that she represents us."
Many of those who heard the speech said they were moved by her message.
"She was fabulous," said Anne Belden, president of Hardy Girls, Healthy
Women, a nonprofit that promotes learning experiences for young women.
"I love the role model she's being for women and girls everywhere."
State Rep. Jeff McCabe, D-Skowhegan, brought his 5-year-old daughter,
Carly, to the fundraiser. They were among a few dozen VIPs who met with
the first lady during a private reception just before she spoke.
McCabe said he was moved when Obama spoke about her husband's commitment
to helping people and promoting opportunity for everyone.
"She talked about how we don't leave people behind," McCabe said. "She
was a dynamic speaker. As good as him if not better."
Around 4 p.m., a seven-car motorcade brought Obama to the Portland
International Jetport. She then flew to a Providence, R.I., for another
fundraising event.
Before today's Ocean Gateway event, Obama attended a smaller fundraiser
at a private home in Cape Elizabeth.
Today ends the year's third-quarter period for campaign finance reports.
Obama for America, the president's re-election campaign committee,
collected more than $47 million in the quarter ending June 30 and is on
track to exceed the $745 million he raised to win election in 2008.
Democrats declined to say how much Michelle Obama raised during her
visit to Maine today.
The crowd included a mixture of young activists and long-time Democrats.
At least two candidates for Portland mayor were there, Mayor Nick
Mavodones Jr. and Michael Brennan. Also there were former Secretary of
State Matt Dunlop, former Attorney General Janet Mills and Kit St. John,
director of the left-leaning Main Center for Economic Policy.
This was Michelle Obama's first visit to Maine since the family
vacationed at Bar Harbor in the summer of 2010. Her husband visited
during the presidential primary four years ago.
Fourteen girls, mostly 11- and 12-year-olds, from the Yarmouth Colts
soccer team, came to get their photograph taken with the first lady.
"We are so excited. Our feet were jittery all day," said Greta Elder,
The White House . 1600 Pennsylvania Avenue, NW . Washington DC 20500 .


text:
Complete Jewish Bible (CJB) | New International Version (NIV) |
1 This is the word that came to Yirmeyahu from ADONAI when King Tzidkiyahu sent to him Pash'chur the son of Malkiyah and Tz'fanyah the son of Ma'aseiyah with this message: | 1 The word came to Jeremiah from the LORD when King Zedekiah sent to him Pashhur son of Malkijah and the priest Zephaniah son of Maaseiah. They said: |
Complete Jewish Bible Copyright 1998 by David H. Stern. Published by Jewish New Testament Publications, Inc. All rights reserved. Used by permission. (The Complete Jewish Bible Online) | Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online) |