prostate cancer ( pca ) is the second most frequent cancer and the fifth leading cause of cancer death in males worldwide . in europe , there are 340 000 new cases and over 70 000 prostate cancer - related deaths reported annually . when detected early , in a prostate gland - localized stage of the disease , biochemical relapse , defined as a psa value > 0.2 ng / ml in patients after radical prostatectomy and a psa level > 2 ng / ml above the nadir psa in patients after radiation therapy , occurs in 2030% of patients after surgical treatment and in up to 60% of patients after primary external - beam therapy [ 3 , 4 ] . the european association of urology ( eau ) recommends a transrectal ultrasound ( trus ) , computed tomography ( ct ) , magnetic resonance imaging ( mri ) and bone scintigraphy ( bs ) for the detection of recurrence sites . however , these conventional imaging modalities are not always effective for an early and reliable detection of pca relapse . bs and ct are of no additional diagnostic value ( detection rate < 5% ) when the psa levels are < 20 ng / ml or the psa velocity is < 2 ng / ml / y . endorectal coil imaging shows utility in local recurrence detection , but only in patients with psa levels > 2 ng / ml . moreover , morphologic imaging ( trus and ct ) sensitivity in detecting local pca relapse remains relatively low ( 2554% ) and is only moderately improved by functional mri techniques . ct and mri sensitivity for the detection of lymph node metastases is reported to be 3080% . the early differentiation between local and metastatic pca is of high importance for patient management . according to the 2013 eau guidelines on prostate cancer , patients with pca recurrence who would benefit the most from salvage radiation therapy ( srt ) are those with psa levels 0.5 ng / ml . the 6-year biochemical recurrence - free survival in these men is 48% , whereas it is only 40% , 28% and 18% in men with psa levels of 0.511 ng / ml , 1.011.5 ng / ml , and > 1.5 ng.ml , respectively . found that patients with a psa level < 0.28 ng / ml before srt had a better outcome than those with higher psa levels and that they may have a chance of a long - term durable response without further treatment . finally , at psa levels > 2 ng / ml , srt is almost ineffective . thus , new molecular imaging modalities with improved specificity and sensitivity for imaging of recurrent pca , especially at low psa levels are of particular clinical interest . in recent years radiocholine positron emission tomography ( pet)/ct has been widely studied and used for pca restaging . compared with 18f - choline , 11c - choline allows for a better evaluation of the pelvic region , because of a lower urinary excretion ( although a greater bowel elimination ) . 18f - choline , on the other hand , has the advantage of being available in centers without a cyclotron ( its half - life is significantly longer than that of 11c - choline , 110 vs. 20 minutes ) and shows a slightly higher sensitivity for bone metastases . many studies have clearly demonstrated that radiocholine pet / ct results can lead to change in treatment . however , radiocholine pet sensitivity strongly depends on psa level and its kinetics . its value for the detection of recurrent pca is limited in patients with psa levels < 2.5 ng / ml [ 9 , 10 ] . in patients with psa / ml the probability of positive radiocholine pet scan is only 19% and may be as low as 12.5% when psa < 0.5 ng / dl . hence , some authors recommend radiocholine pet imaging in patients with pca biochemical relapse only when the psa level is higher than 1.5 ng / ml , psa velocity exceeds 0.75 ng / ml / y , or psa doubling time is shorter than 6 months [ 8 , 10 ] . since biochemical relapse is already suspected when psa level exceeds 0.2 ng / ml , there is a high demand for more sensitive pet radiotracers . radiotracers targeting markers of pca cells show huge promise in the field and prostate - specific membrane antigen ( psma ) seems to be receiving the greatest attention . psma is a type ii , 750-amino - acid integral membrane glycoprotein ( 100120 kda ) , with a 19-amino - acid n - terminal cytoplasmic tail , a 24-amino - acid helical intramembrane segment , and a large 707-amino - acid extracellular c - terminus [ 12 , 13 ] . the extracellular domain of the psma has an enzymatic activity of glutamate - carboxypeptidase / folate hydrolase and is only active as a dimer . following substrate binding , psma - bound ligands are internalized via clathrin - coated pits , endocyted and transported into the cell . its gene ( folh1 ) is located on the short arm of chromosome 11 . despite its name , psma is not specific to the prostate gland and is expressed in other normal tissues such as the salivary and lacrimal glands , kidney ( proximal tubules ) , liver , spleen , nervous system glia ( astrocytes and schwann cells ) , duodenum ( brush border ) and the colon ( neuroendocrine cells of the crypts ) . at the jejnual border psma , called folate hydrolase 1 , assists in the folate absorption [ 1619 ] . in the nervous system , psma has been termed naaladase and is responsible for hydrolyzing n - acetyl aspartylglutamate ( naag ) , the third - most - prevalent peptide neurotransmitter in the mammalian nervous system . although psma had been first discovered in the prostate in 1987 , its role in the gland is still not well - defined . yet it seems psma may be involved in releasing folates into the seminal fluid . in the normal human prostate psma is present in the cytoplasm and expressed on the apical side of the epithelium surrounding the prostatic ducts . dysplastic changes in the prostate result in the expression of psma on the luminal surface of prostatic ducts [ 22 , 23 ] . its expression has been also shown to increase from benign prostatic hyperplasia to high - grade prostatic intraepithelial neoplasia to prostatic adenocarcinoma , where it reaches 1001000-fold of what is observed in the normal prostate cells [ 24 , 25 ] . it has been reported that nearly all prostate adenocarcinomas ( primary tumors as well as metastatic lesions ) show psma expression . sweat et al . reported only 2% psma - negative lymph node metastases of pca . it was also found that the higher the gleason score of the primary lesion , the higher the psma expression [ 28 , 29 , 30 ] . high psma expression is also associated with propensity to metastasize , androgen independence and disease progression [ 29 , 31 , 32 ] . apart from prostate cancer , the psma presence has been also confirmed in kidney and bladder cancer as well as numerous non - genitourinary cancers , such as breast and colon cancer [ 3339 ] . the favorable characteristics of psma ( overexpression in pca cells and ligand - enzyme complex internalization after ligand binding ) have led to the development of molecular imaging agents targeting the enzyme . however , they showed disappointing results due to the low image contrast , low sensitivity , and high background signal . more recently , new psma - targeted agents such as small - molecule inhibitors ( targeting the extracellular domain of psma ) have been developed and extensively studied [ 38 , 39 ] . they have been labeled with many radionuclides including 11c , 18f , 89zr , 64cu , 86y , and 68ga . however , it is 68ga - psma ( glu - nh - co - nh - lys-(ahx)-[68ga(hbed - cc ) ] ) that receives the greatest attention . in this agent hbed - cc moiety chelates the 68ga radiometal and is conjugated through a linker with a urea that binds in the active site of psma . 68ga is produced by a tabletop 68ge/68ga generator which makes it an attractive radionuclide , especially for pet centers that do not operate a cyclotron . biochemical recurrence following local therapy has been the most extensively studied application of psma - based imaging . the two largest reported studies were by afshar - oromieh et al . and eiber et al . retrospectively assessed 68ga - psma pet / ct results of patients with suspected pca progression after radical treatment and found at least one lesion indicative of pca in 82.8% of cases . lesion detection rate correlated positively with psa level ( sensitivity for psa values 0.5 ng / ml was 48.1% and for values > 20.0 ng / ml it reached 100.0% ) and adt . however , it was not correlated with primary tumor gleason score and psadt . in a subset of lesions for which histology was available , 68-ga psma pet - positivity was also correlated with psa levels  the authors showed a detection rate of 60% at psa < 2.2 ng / ml and 100% at psa > 2.2 ng / ml . correspondingly , in a retrospective study by demirkol et al . none of the 68ga - psma pet / ct scans revealed negative results in patients with psa levels above 2 ng / ml . in a retrospective study by eiber et al . patients with pca biochemical recurrence after radical prostatectomy were assessed . similarly to afshar - oromieh et al . , detection rate was 89.5% and it correlated positively with serum psa levels rising from 57.9% in patients with psa < 0.5 ng / ml to 96.8% in patients with psa 2.0 ng / ml . no significant association was found for psadt , yet psa velocity did increase the detection rate . , eiber et al . found that primary lesion gleason score ( 7 vs. 8 ) significantly increased detection rate . the authors did not observe significant differences in detection rate with regard to adt ( lesions were detected in 95.7% of patients with adt vs. 87.1% without adt ) . also reported that 33% of lesions were observed in pet only ( not suspicious in ct ) and that in 25% of cases pet revealed more lesions than ct . have evaluated 70 patients after rp or rt with curative intent and biochemical relapse or persisting high psa levels after primary treatment . correspondingly to afshar - oromieh et al . and eiber et al . psadt was also showed to have a significant impact on 68ga - psma pet / ct sensitivity . psa level , ongoing adt , patient s age , gs , time from primary therapy and pca tnm staging , on the other hand , were not associated with pet / ct positivity . roc analysis showed that psadt of 6.5 months ( auc 0.868 ) and psa level of 0.83 ng / ml ( auc 0.764 ) were optimal cut - off values for predicting with high probability of a positive or negative pet / ct scan result . the overall percentage of positive 68ga - psma pet among patients with biochemical recurrence in a systematic review and meta - analysis by perera et al . 68ga - psma pet detection rate increased with pre - pet psa and was higher the higher the psa levels ( 00.2 ng.ml : 42% , 0.21 ng / ml : 58% , 12 ng / ml : 76% , > 2 ng / ml : 95% ) . 68ga - psma pet positivity increased with shorter psadt and for psadt 6 months and < 6 months equalled 64% and 92% , respectively . the results of the above studies support the application of 68ga - psma pet / ct in the diagnosis of pca biochemical recurrence . yet it must be emphasized that the majority of gathered data was derived from small , retrospective studies with heterogenous patient cohorts ( table 1 ) . characteristics of the studies investigating the utility of 68ga - psma pet / ct in recurrent prostate cancer adt  androgen deprivation therapy ; bcr  biochemical recurrence ; gs  gleason score ; psadt  psa doubling time ; psavel  psa velocity ; pt  primary therapy ; tnm  tumour - node - metastasis several groups have directly compared 68ga - psma to radiocholines in the detection of biochemically recurrent pca . the authors found a higher detection rate for pca lesions with 68ga - psma than 18f - fluoromethylcholine ( 86.5% vs. 70.3% ) . 68ga - psma proved superior to 18f - fluoromethylcholine pet / ct especially at low psa levels  for psa levels 2.82 ng / ml the sensitivity was 68.8% vs. 43.8% , respectively ( table 2 ) . 68ga - psma was also reported to show superior radiotracer uptake and tumor - to - background ratio . accuracy ; bcr  biochemical recurrence ; npv  negative predictive value ; ppv  positive predictive value all psa levels are given in ng / ml in a prospective study by morigi et al . 18f - fluoromethylcholine and 68ga - psma pet / ct was performed in patients after curative therapy who developed a post - therapy psa rise . similarly to afshar - oromieh et al . , psma - targeted radiotracer showed higher pca lesion detection rates than 18f - fluoromethylcholine and its superiority was demonstrated across all psa values detection rate varied from 50% vs. 12.5% for psa levels < 0.5 ng / ml and to 88% vs. 63% for psa levels > 2.0 ng / ml ( table 2 ) . additionally , 68ga - psma - based scans detected more lesions and showed higher tumor - to - background ratio . correspondingly to previous studies , the authors found that the most significant predictor for positive pet result for both 18f - fluoromethylcholine and 68ga - psma was psa level at the time of imaging . reported that 68ga - psma pet / ct impact on patients management was exceptionally high , especially when the scan was performed at low absolute psa levels . reported that 68ga - psma pet / ct detects disease in 43.8% of patients with biochemical pca recurrence , but negative 18f - choline scans . sequential imaging ( performing 68ga - psma pet / ct after negative choline scans ) increased detection rate by 11.2% ( from 74.4% to 85.6% ) ( table 2 ) . 68ga - psma pet / ct detection rates were 28.6% , 45.5% and 71.4% for psa levels of 0.2 to < 1 ng / ml , 1 - 2 ng / ml and > 2 ng / ml , respectively . similarly , in a retrospective study pfister et al . demonstrated superior performance for 68ga - psma pet compared to 18f - fluoroethylcholine pet among patients with biochemical recurrence . sensitivity and specificity for 68ga - psma and 18f - fluoroethylcholine were 86.9% vs. 71.2% and 93.1% vs. 86.9% , respectively   ( table 2 ) . have assessed the utility of 68ga - psma and 11c - choline pet / ct in patients with pca biochemical relapse . compared to choline radiotracer , 68ga - psma showed higher detection rate for both lymph node ( 71% vs. 94% ) and bone metastases ( 64% vs. 98% ) . the overall detection rate was 83% in 68ga - psma and 79% in 11c - choline pet ( table 2 ) . additionally , pathologic lesions showed a significantly higher radiotracer uptake in 68ga - psma pet than in 11c - choline pet . psma - based radiotracer superiority was more marked in patients with low psa levels ( < 1 ng / ml ) . to our knowledge , the study by schwenck et al . is the only direct comparison of 68ga - psma and 11c - choline pet performed so far . the results of the studies comparing radiocholines and 68ga - psma pet / ct for the diagnosis of recurrent pca are very promising for the latter one . psma - based scans show higher sensitivity and specificity , especially at low psa levels . tumour lesions also show higher 68ga - psma uptake and higher tumour - to - background ratio . however , the number of studies comparing 68ga - psma and radiocholines is limited and the majority of data comes from retrospective analyses . psma is a type ii , 750-amino - acid integral membrane glycoprotein ( 100120 kda ) , with a 19-amino - acid n - terminal cytoplasmic tail , a 24-amino - acid helical intramembrane segment , and a large 707-amino - acid extracellular c - terminus [ 12 , 13 ] . the extracellular domain of the psma has an enzymatic activity of glutamate - carboxypeptidase / folate hydrolase and is only active as a dimer . following substrate binding , psma - bound ligands are internalized via clathrin - coated pits , endocyted and transported into the cell . its gene ( folh1 ) is located on the short arm of chromosome 11 . despite its name , psma is not specific to the prostate gland and is expressed in other normal tissues such as the salivary and lacrimal glands , kidney ( proximal tubules ) , liver , spleen , nervous system glia ( astrocytes and schwann cells ) , duodenum ( brush border ) and the colon ( neuroendocrine cells of the crypts ) . at the jejnual border psma , called folate hydrolase 1 , assists in the folate absorption [ 1619 ] . in the nervous system , psma has been termed naaladase and is responsible for hydrolyzing n - acetyl aspartylglutamate ( naag ) , the third - most - prevalent peptide neurotransmitter in the mammalian nervous system . although psma had been first discovered in the prostate in 1987 , its role in the gland is still not well - defined . yet it seems psma may be involved in releasing folates into the seminal fluid . in the normal human prostate psma is present in the cytoplasm and expressed on the apical side of the epithelium surrounding the prostatic ducts . dysplastic changes in the prostate result in the expression of psma on the luminal surface of prostatic ducts [ 22 , 23 ] . its expression has been also shown to increase from benign prostatic hyperplasia to high - grade prostatic intraepithelial neoplasia to prostatic adenocarcinoma , where it reaches 1001000-fold of what is observed in the normal prostate cells [ 24 , 25 ] . it has been reported that nearly all prostate adenocarcinomas ( primary tumors as well as metastatic lesions ) show psma expression . according to the study by mannweiler et al . sweat et al . reported only 2% psma - negative lymph node metastases of pca . it was also found that the higher the gleason score of the primary lesion , the higher the psma expression [ 28 , 29 , 30 ] . high psma expression is also associated with propensity to metastasize , androgen independence and disease progression [ 29 , 31 , 32 ] . apart from prostate cancer , the psma presence has been also confirmed in kidney and bladder cancer as well as numerous non - genitourinary cancers , such as breast and colon cancer [ 3339 ] . the favorable characteristics of psma ( overexpression in pca cells and ligand - enzyme complex internalization after ligand binding ) have led to the development of molecular imaging agents targeting the enzyme . however , they showed disappointing results due to the low image contrast , low sensitivity , and high background signal . more recently , new psma - targeted agents such as small - molecule inhibitors ( targeting the extracellular domain of psma ) have been developed and extensively studied [ 38 , 39 ] . they have been labeled with many radionuclides including 11c , 18f , 89zr , 64cu , 86y , and 68ga . however , it is 68ga - psma ( glu - nh - co - nh - lys-(ahx)-[68ga(hbed - cc ) ] ) that receives the greatest attention . in this agent hbed - cc moiety chelates the 68ga radiometal and is conjugated through a linker with a urea that binds in the active site of psma . 68ga is produced by a tabletop 68ge/68ga generator which makes it an attractive radionuclide , especially for pet centers that do not operate a cyclotron . biochemical recurrence following local therapy has been the most extensively studied application of psma - based imaging . the two largest reported studies were by afshar - oromieh et al . and eiber et al . retrospectively assessed 68ga - psma pet / ct results of patients with suspected pca progression after radical treatment and found at least one lesion indicative of pca in 82.8% of cases . lesion detection rate correlated positively with psa level ( sensitivity for psa values 0.5 ng / ml was 48.1% and for values > 20.0 ng / ml it reached 100.0% ) and adt . however , it was not correlated with primary tumor gleason score and psadt . in a subset of lesions for which histology was available , 68-ga psma pet - positivity was also correlated with psa levels  the authors showed a detection rate of 60% at psa < 2.2 ng / ml and 100% at psa > 2.2 ng / ml . correspondingly , in a retrospective study by demirkol et al . none of the 68ga - psma pet / ct scans revealed negative results in patients with psa levels above 2 ng / ml . in a retrospective study by eiber et al . patients with pca biochemical recurrence after radical prostatectomy were assessed . similarly to afshar - oromieh et al . , detection rate was 89.5% and it correlated positively with serum psa levels rising from 57.9% in patients with psa < 0.5 ng / ml to 96.8% in patients with psa 2.0 ng / ml . no significant association was found for psadt , yet psa velocity did increase the detection rate . , eiber et al . found that primary lesion gleason score ( 7 vs. 8 ) significantly increased detection rate . the authors did not observe significant differences in detection rate with regard to adt ( lesions were detected in 95.7% of patients with adt vs. 87.1% without adt ) . also reported that 33% of lesions were observed in pet only ( not suspicious in ct ) and that in 25% of cases pet revealed more lesions than ct . have evaluated 70 patients after rp or rt with curative intent and biochemical relapse or persisting high psa levels after primary treatment . correspondingly to afshar - oromieh et al . and eiber et al . psadt was also showed to have a significant impact on 68ga - psma pet / ct sensitivity . psa level , ongoing adt , patient s age , gs , time from primary therapy and pca tnm staging , on the other hand , were not associated with pet / ct positivity . roc analysis showed that psadt of 6.5 months ( auc 0.868 ) and psa level of 0.83 ng / ml ( auc 0.764 ) were optimal cut - off values for predicting with high probability of a positive or negative pet / ct scan result . the overall percentage of positive 68ga - psma pet among patients with biochemical recurrence in a systematic review and meta - analysis by perera et al . 68ga - psma pet detection rate increased with pre - pet psa and was higher the higher the psa levels ( 00.2 ng.ml : 42% , 0.21 ng / ml : 58% , 12 ng / ml : 76% , > 2 ng / ml : 95% ) . 68ga - psma pet positivity increased with shorter psadt and for psadt 6 months and < 6 months equalled 64% and 92% , respectively . the results of the above studies support the application of 68ga - psma pet / ct in the diagnosis of pca biochemical recurrence . yet it must be emphasized that the majority of gathered data was derived from small , retrospective studies with heterogenous patient cohorts ( table 1 ) . characteristics of the studies investigating the utility of 68ga - psma pet / ct in recurrent prostate cancer adt  androgen deprivation therapy ; bcr  biochemical recurrence ; gs  gleason score ; psadt psa doubling time ; psavel  psa velocity ; pt  primary therapy ; tnm  tumour - node - metastasis several groups have directly compared 68ga - psma to radiocholines in the detection of biochemically recurrent pca . the authors found a higher detection rate for pca lesions with 68ga - psma than 18f - fluoromethylcholine ( 86.5% vs. 70.3% ) . 68ga - psma proved superior to 18f - fluoromethylcholine pet / ct especially at low psa levels  for psa levels 2.82 ng / ml the sensitivity was 68.8% vs. 43.8% , respectively ( table 2 ) . 68ga - psma was also reported to show superior radiotracer uptake and tumor - to - background ratio . characteristics of the comparative studies included in this section acc  accuracy ; bcr  biochemical recurrence ; npv  negative predictive value ; ppv  positive predictive value all psa levels are given in ng / ml in a prospective study by morigi et al . 18f - fluoromethylcholine and 68ga - psma pet / ct was performed in patients after curative therapy who developed a post - therapy psa rise . similarly to afshar - oromieh et al . , psma - targeted radiotracer showed higher pca lesion detection rates than 18f - fluoromethylcholine and its superiority was demonstrated across all psa values detection rate varied from 50% vs. 12.5% for psa levels < 0.5 ng / ml and to 88% vs. 63% for psa levels > 2.0 ng / ml ( table 2 ) . additionally , 68ga - psma - based scans detected more lesions and showed higher tumor - to - background ratio . correspondingly to previous studies , the authors found that the most significant predictor for positive pet result for both 18f - fluoromethylcholine and 68ga - psma was psa level at the time of imaging . reported that 68ga - psma pet / ct impact on patients management was exceptionally high , especially when the scan was performed at low absolute psa levels . reported that 68ga - psma pet / ct detects disease in 43.8% of patients with biochemical pca recurrence , but negative 18f - choline scans . sequential imaging ( performing 68ga - psma pet / ct after negative choline scans ) increased detection rate by 11.2% ( from 74.4% to 85.6% ) ( table 2 ) . 68ga - psma pet / ct detection rates were 28.6% , 45.5% and 71.4% for psa levels of 0.2 to < 1 ng / ml , 1 - 2 ng / ml and > 2 ng / ml , respectively . similarly , in a retrospective study pfister et al . demonstrated superior performance for 68ga - psma pet compared to 18f - fluoroethylcholine pet among patients with biochemical recurrence . sensitivity and specificity for 68ga - psma and 18f - fluoroethylcholine were 86.9% vs. 71.2% and 93.1% vs. 86.9% , respectively   ( table 2 ) . have assessed the utility of 68ga - psma and 11c - choline pet / ct in patients with pca biochemical relapse . compared to choline radiotracer , 68ga - psma showed higher detection rate for both lymph node ( 71% vs. 94% ) and bone metastases ( 64% vs. 98% ) . the overall detection rate was 83% in 68ga - psma and 79% in 11c - choline pet ( table 2 ) . additionally , pathologic lesions showed a significantly higher radiotracer uptake in 68ga - psma pet than in 11c - choline pet . psma - based radiotracer superiority was more marked in patients with low psa levels ( < 1 ng / ml ) . to our knowledge , the study by schwenck et al . is the only direct comparison of 68ga - psma and 11c - choline pet performed so far . the results of the studies comparing radiocholines and 68ga - psma pet / ct for the diagnosis of recurrent pca are very promising for the latter one . psma - based scans show higher sensitivity and specificity , especially at low psa levels . tumour lesions also show higher 68ga - psma uptake and higher tumour - to - background ratio . however , the number of studies comparing 68ga - psma and radiocholines is limited and the majority of data comes from retrospective analyses . the growing need for accurate imaging of early pca recurrence has prompted the introduction of 68ga - psma pet . although a limited number of studies is available , the results support the use of 68ga - psma pet in the context of secondary pca staging . moreover , psma - based pet scans have so far been proven to provide superior diagnostic performance than any other modality ( including radiocholine pet / ct ) for localisation of the site of early pca recurrence . however , owing to its limited history robust sensitivity and specificity , data are not available for 68ga - psma pet / ct scans . also , most psma - assessing research were small , retrospective , single - institutional studies with heterogenous patient cohorts . only few studies compared 68ga - psma performance with established radiotracers such as radiocholines . large , multidisciplinary , well - thought - out prospective trials are needed to definitely uncover the true utility of psma - based pet in pca recurrence diagnosis . despite significant advances , there is a considerable scope for further research in psma pet .
introductionprostate cancer ( pca ) is a major health concern worldwide with up to 60% of patients experiencing biochemical relapse after radical treatment . 
 early diagnosis of pca recurrence is of high importance for successful salvage therapy . 
 the need for accurate imaging has prompted the introduction of prostate - specific membrane antigen ( psma)-based radiotracers for positron emission tomography ( pet).material and methodsin this review we summarized and discussed the results of the studies analyzing the utility of 68ga - psma pet / ct in patients who experienced a biochemical relapse of prostate cancer.resultspsma-based pet scans have been proved to provide a superior diagnostic performance over other modalities for localization of the site of early pca recurrence . 
 68ga - psma has been also shown to have a higher sensitivity and specificity than other established pet radiotracers such as radiocholines.conclusionsthe early studies show promising results and support the use of 68ga - psma for pca restaging . 
 however , the number of studies concerning the utility of 68ga - psma pet in the context of secondary pca staging is limited and there is still a considerable scope for further research in this field .