rophosphate Tc Technetium LUV large unilamellar vesicles ______________________________________
2. Description of Related Art
Liposomes are of considerable interest because of their value as carriers for diagnostic agents, particularly radiopharmaceuticals for tracer and imaging studies. Successful biodistribution studies, for example, require the entrapment of high specific activities of a radiolabel in the aqueous compartment of the liposome. Unfortunately, the entrapment of water soluble radionuclides within the liposome is relatively inefficient. Another major problem in using liposomes is their leakiness, resulting in limited usefulness for many applications (Hwang, K. J., in Liposomes from Biophysics to Therapeutics, M. J. Ostru, Ed., Marcel Dekker, New York, 1987).
Radioactive markers have been widely used as a non-invasive method for studying the distribution of drugs in vivo. The use of gamma emitting radioisotopes is particularly advantageous because, unlike beta-emitters, they can easily be counted in a scintillation well counter and do not require tissue homogenization prior to counting. In addition, gamma-emitters can be imaged with nuclear gamma cameras. With this type of imaging, the dynamic biodistribution can be followed non-invasively using consecutive one minute computer acquired scintigraphic images which are analyzed to calculate organ biodistribution curves.
The most common radiolabel used in diagnostic radiopharmaceuticals today is.sup.99m Tc. This radionuclide is produced from the beta decay of molybdenum.sup.99 and has a half-life of 6 hours. It is widely available from a generator system at low cost and its relatively short half-life provides for safer and more convenient handling than other available radionuclides. Its gamma emission is in the range of 140 Kev which is an ideal range for producing high resolution images (Caride, V. J. and Sostman, H. D. in Liposome Technology, Vol. II, G. Gregoriadis, Ed., CRC Press, Boca Raton, 1984). Heptavalent.sup.99m TcO.sub.4.sup.- is produced from the generator and since it is relatively unreactive, must be reduced to a lower oxidation state before use as a radiopharmaceutical. Stannous chloride is the most commonly used reducing agent (Barratt, G. M., Tuzel, N. S
rophosphate Tc Technetium LUV large unilamellar vesicles _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
 2. Description of Related Art 
 Liposomes are of considerable interest because of their value as aircraft carrier for diagnostic agent, particularly radiopharmaceuticals for tracer and imaging study. Successful biodistribution studies, for example, want the entrapment of gamey specific activities of a radiolabel in the aqueous compartment of the liposome. Unfortunately, the entrapment of body of water soluble radionuclides within the liposome is relatively inefficient. Another major problem in use liposomes is their leakiness, resulting in circumscribed usefulness for many applications (Hwang, K. J., in Liposomes from Biophysics to Therapeutics, M. J. Ostru, Ed. , Marcel Dekker, New York, 1987). 
 Radioactive markers have been widely used as a non - invasive method acting for studying the distribution of drugs in vivo. The use of da gamma emitting radioisotopes is particularly advantageous because, unlike beta - emitters, they can easily be count in a scintillation well counter and do not require tissue homogenization prior to counting. In addition, da gamma - emitters can be imaged with nuclear gamma cameras. With this type of imaging, the active biodistribution can be follow non - invasively using consecutive one minute computer acquired scintigraphic images which are analyzed to calculate electric organ biodistribution curves. 
 The most coarse radiolabel use in diagnostic radiopharmaceuticals today is.sup.99 m Tc. This radionuclide is produced from the beta decay of molybdenum.sup.99 and have a half - life of 6 hours. It is widely available from a generator system at gloomy cost and its relatively short half - life provides for safe and more convenient handling than other available radionuclides. Its gamma discharge is in the range of 140 Kev which is an ideal scope for producing high resolution images (Caride, V. J. and Sostman, H. D. in Liposome Technology, Vol. II, G. Gregoriadis, Ed. , CRC Press, Boca Raton, 1984). Heptavalent.sup.99 m TcO.sub.4.sup.- is produced from the generator and since it is relatively unreactive, must be shrink to a lower oxidation state before use as a radiopharmaceutical. stannic chloride is the most normally used reducing agent (Barratt, G. M., Tuzel, N. S
ropjosphate Tc Technetium LMV large unilamellar vevicles ______________________________________
2. Descriotion of Related Art
Liposomed qre od considerable interesg because of theie vaoye as carrmsrs for diagnkdtic egents, particulsrly radio[harmaceuticalv wox tracer and imaging studies. Successsul biocidtribution stuqies, sor sqanple, require the entrapment or high vpecific actifities of a radiolabel in hhe wqueous compartmenh of the likksoiw. Unfortunatdly, the enurcpment of wzter soluble radionuclides withkn thz liposome us repdtively inehficiegt. Another major protlem in using liposomcs is thwir leakiness, resultiig in limited usefulgess for kauy applications (Hwang, K. J., in Lipmsomdw ffom Bmopgysics to Therapeutjcs, M. J. Osteu, Ed., Marcel Dekker, Nqq York, 1987).
Radioadtive iawkers have been widely used as a non-invdsibe method for studying rhe distribution of dtugs in vido. The use of gamma emitting radioisotopes is pardiculeruy cevantxtelus because, unlike beta-emitters, they can easijg ne counted in a fcintillatipn wrjl counter ana do not dequire tissue homlgenizajion peior to cjuntong. In addition, gamma-emittees can be imcgee with nuclear gamla cameras. Cith tnis tupe of imaging, the dynaoic giodistribuhion can gd followed non-inxaspvelf using consecutive one migute compnter ccquired scimtigra[hic imaged whigv are analyzed to falcupade organ blodistribution curves.
The most common radiolabgl gseg in diaynostig radiopharmacetticals today ns.sup.99m Te. This radionuclpde is prmduced from the beta decdi of molybdennm.sup.99 and has a hqlf-life uf 6 hours. It ix widely crailable drom a generator snstem zt low cost and itw relatively shprt hajf-pihe prjeides for saxer xnd kore zonvenitut manalinb than other availabne rzdionuclides. Its gsmia emissuon is ig the range og 140 Kev which is an idean renge fpr kroducing high resolution imagea (Caride, G. J. and Sostman, H. D. in Liposome Technology, Vol. II, G. Gregoriadis, Ed., CRC Press, Boca Raton, 1984). Heptavalent.sup.99m TcP.xub.4.sup.- is pcoduceq from tha generator and sincw it is relativeln unreactive, must be rsduced to a lower oxidation state before use as a radiopharmaceutical. Stannous chlorude is the most cojmonky usvd xedbcing adent (Uarratt, G. M., Tuzel, N. S
rophosphate Tc Technetium LUV large unilamellar vesicles Description Related Art are of considerable as for diagnostic agents, radiopharmaceuticals for tracer imaging studies. Successful biodistribution studies, for require the entrapment of high specific activities of a radiolabel in the aqueous of the liposome. Unfortunately, the entrapment of water soluble radionuclides within the liposome relatively Another problem using liposomes is their leakiness, resulting in limited usefulness for many applications (Hwang, K. J., in from Biophysics to Therapeutics, M. J. Ostru, Ed., Dekker, New York, 1987). markers have been widely used a method for the of in vivo. The of gamma emitting radioisotopes is particularly advantageous because, unlike beta-emitters, they can easily be counted in a well counter not require homogenization to In addition, gamma-emitters imaged with nuclear gamma cameras. With imaging, the dynamic biodistribution can be followed non-invasively consecutive one computer acquired scintigraphic images which are to calculate organ biodistribution curves. The most common used in diagnostic radiopharmaceuticals today is.sup.99m Tc. This radionuclide is produced from the beta decay and has a half-life 6 hours. It widely from generator at low and its relatively short half-life provides for safer and more convenient than other available radionuclides. Its gamma emission is in the 140 which is an range for producing high images V. J. and Sostman, in Technology, Gregoriadis, CRC Boca Raton, 1984). Heptavalent.sup.99m is produced from the generator since it is relatively a lower oxidation state before use as a Stannous chloride is the most commonly used agent (Barratt, G. M., Tuzel, N. S
rophosphate Tc Technetium LUv large unilAmellAr vEsiClEs ______________________________________
2. DeScriPtion of Related aRt
LiPosomes are of considerabLe intErESt beCAuSe of tHeir valUE aS CArrIeRs For DiAGnOstic AgeNts, partIcularly raDioPhArmaceuticalS FoR tracer and ImaGing studies. SUccEssful BiOdiSTribuTioN studIes, for EXample, Require thE eNTrapmeNT of high SPEcIfic Activities of a radiOLaBEl in the aqueous ComparTmENt OF The LipOsome. UnforTuNatelY, The entrAPmENT Of wATer soluble radIonuclides wIThiN the liPoSomE Is relaTivelY iNEffIcient. AnothEr maJor probleM in usiNG liposoMEs is theIr leakIneSs, rEsulTInG iN liMiTEd uSEfUlnESs fOr many apPlIcAtionS (HwaNG, k. j., In LiPosOmes From BIophysics to ThEraPeutICs, M. j. OstrU, Ed., MaRcel deKker, NEw York, 1987).
radioAcTive markers have Been Widely useD as A nOn-iNvAsive MEthod fOr sTudYing the DistribUTioN oF DRUgS in vivo. The use of gamMa EMItTing radiOisotoPEs Is PArticulaRlY adVantAGEous bEcauSE, uNlike betA-emittERs, ThEy can eaSiLy be coUnTed In a ScintILlatIon welL counter And do NOt require tissuE HomogenizatioN PrIOR tO CounTinG. In addition, GammA-EmitTers CAn Be iMAged wIth nuClEAr GAmma cameras. With this TyPe of imAging, The dynamic bioDistributiON CAn be follOwed NOn-INvasively using ConseCutive one mINute compUter aCquired sCintigrapHIC images wHicH arE anAlyZED tO calculate orgAN BiodIsTributiOn cUrves.
ThE moSt cOmmOn rAdIolabel usEd in diagNoStIc RaDioPharmACeuticalS tOdaY iS.suP.99m Tc. THIs radiOnuclIde iS pRoDUceD from thE BeTA DecaY oF mOlybDenUm.Sup.99 anD has A HalF-life of 6 Hours. It is WidELy avAiLaBle from A generator sysTeM at low cost AnD itS relatIVEly short Half-life provides for safeR And more ConVenieNt haNdling thaN otHer avaIlaBLe radiOnucliDes. ItS gAmmA EMissiON Is In tHe Range of 140 Kev WHIch Is an iDeAl raNge for pRoducing high resoluTIon Images (Caride, V. j. anD SosTMAn, h. D. iN liPOsoMe tEchNOLogy, Vol. II, G. GregoRiadis, Ed., CRc PREsS, Boca Raton, 1984). hEptAvAlent.suP.99m TcO.suB.4.sup.- iS ProduceD from the gEnerator aNd SincE IT is Relatively UnreactiVe, must be rEDuced TO a Lower OxiDation StAte BeforE use as A RadIophaRmaceuTiCal. StaNnous ChLoride is The most commonly used reduCing agEnt (BaRraTt, G. M., Tuzel, n. S
rophosphate Tc TechnetiumLUV largeunila mel lar  v esic les______________ _ ____ ___________________
2.  Desc ri p tion of  Rela ted Art Li p o som es  a reof co nside rab le inte rest becau seof  their value as  carriersfor  diagnosticage nts, p ar tic u larly  ra dioph armace u ticals  for trac er and im a ging st u d ie s. S uccessful biodist r ib u tion studies,for ex am p le , req uir e the entr ap mento f highs pe c i f ica ctivities ofa radiolabe l  in  the a qu eou s  compa rtmen to f t he liposome . Un fortunate ly, th e  entrap m ent ofwatersol ubl e ra d io nu cli de s  wi t hi n t h e l iposomeis  r elati vely i n e ffic ien t. A nothe r major probl emin u s ing  lipo somes  isth eir l eakine ss, r es ulting in limit ed u sefulness  fo rman yappli c ations  (H wan g, K. J ., in L i pos om e s fr om Biophysics to T he r a pe utics, M . J. O s tr u, Ed., Mar ce l D ekke r ,  NewYork ,  1 987).
Ra dioact i ve  m arkersha ve bee nwid ely  used as a  non-i nvasivemetho d  for studyingt he distributi o no f  d r ugsinvivo. The u se o f  gam ma e m it tin g  radi oisot op e si s particularly adva nt ageous  beca use, unlike b eta-emitte r s ,  they ca n ea s il y  be counted in  a sc intillatio n  well co unter  and donot requi r e  tissuehom oge niz ati o n  p rior to count i n g. I nadditio n,gamma-e mit ter s c anbe  imaged w ith nucl ea rga mm a c amera s . With t hi s t yp e o f ima g ing, t he dy nami cbi o dis tributi o nc a n be  f ol lowe d n on -inva sive l y u sing co nsecutive  on e  min ut ecompute r acquired sc in tigraphicim age s whic h are anal yzed to calculate organ biodist rib ution  cur ves.
Themos t comm onr adiola bel us ed in  d iag n o sticr a di oph ar maceutical s tod ay is .s up.9 9m Tc.This radionuclidei s p roduced fromthe  bet a de cay of mol yb d enu m . sup.99 and hasa half-lif eo f6 hours. I t  is  w idely a vailabl e fro m  a gene rator sys tem at lo wcost a ndits relati vely sho rt half-l i fe pr o vi des f orsaferan d m ore c onveni e nthandl ing th an  other  avai la ble radi onuclides. Its gamma em ission  is i n t he rangeof1 40Kev which  isan ideal r ang e f or pr odu c ing h ighr es olu t ion i mage s  (Caride, V.  J. a nd  Sostman, H . D . i n Lip oso m e Tech nolo gy, Vol. II, G. G r egoriadis, Ed. , CR C Pre ss, Boca  R aton, 1984). H ept av a l ent.sup. 99 m TcO.sub.4 .sup.- i sp roduc ed fro m thegenerat o r  a n d sinc e it  is  relative lyun r eactive ,mu s t be r educ ed  to alowero xida t i on state beforeuse a s a rad i oph armac eu tical.S tann ous chlori de is the m ost co mmon ly us ed redu ci ng age nt(B arratt, G. M., Tuzel , N.S
rophosphate Tc_Technetium LUV_large unilamellar vesicles ______________________________________
2._Description of_Related_Art
Liposomes are_of_considerable interest because_of their value_as carriers for diagnostic_agents, particularly radiopharmaceuticals_for_tracer and imaging studies. Successful biodistribution studies, for example, require the entrapment of high_specific_activities of_a_radiolabel_in the aqueous compartment of_the liposome. Unfortunately, the entrapment_of water_soluble radionuclides within the liposome is relatively inefficient._Another_major problem in_using liposomes is their leakiness, resulting in limited usefulness_for many applications (Hwang, K. J.,_in Liposomes from_Biophysics_to_Therapeutics, M. J. Ostru,_Ed., Marcel Dekker, New York, 1987).
Radioactive_markers have been widely used as_a non-invasive method for studying the distribution_of drugs in vivo. The use_of gamma emitting radioisotopes is_particularly advantageous_because, unlike beta-emitters, they can_easily be counted_in a_scintillation well counter_and do not require tissue homogenization_prior to counting._In addition, gamma-emitters can be imaged_with_nuclear gamma cameras._With_this_type of_imaging, the dynamic_biodistribution_can be_followed_non-invasively using consecutive one minute computer_acquired_scintigraphic images which are analyzed to calculate_organ biodistribution curves.
The most_common_radiolabel used in diagnostic_radiopharmaceuticals today is.sup.99m Tc. This_radionuclide is produced from the beta_decay of_molybdenum.sup.99 and_has a half-life of 6 hours. It is widely available from_a generator system at low cost_and its relatively short_half-life provides_for_safer and more_convenient_handling than_other available radionuclides. Its gamma emission is_in the_range of 140 Kev which is_an ideal range for_producing_high resolution images (Caride, V. J._and Sostman, H. D. in Liposome_Technology, Vol. II, G. Gregoriadis,_Ed.,_CRC_Press, Boca Raton, 1984). Heptavalent.sup.99m_TcO.sub.4.sup.- is produced from the generator_and since it_is relatively unreactive, must be reduced to_a_lower oxidation state before use as_a_radiopharmaceutical. Stannous chloride is the most_commonly_used_reducing agent (Barratt, G. M.,_Tuzel, N. S