Tumor Receptor Imaging Agent - ~ (99) ~ Tcm-tricine-hynic-tyr ~ 3-octreotide Development

Over the past two decades, radiolabelled peptide has been emerged as anew, useful class of radiopharmceuticals for diagnosis of a variety ofendocrine tumors, in particular, about the research of somatostatin and itsanalogues. Although till today,⁹⁰Y-DOTA-Tyr³-Octreotide and ¹¹¹In-DTPA-Octreotide and ¹²³I-VIP have been applied in clinics, extensiveefforts have been made in preparing and evaluating peptides labelled with⁹⁹Tc^m by virtue of its cost-effectiveness, availability and desirable nuclearcharacters. In this paper, the development and evaluation of ⁹⁹Tc^m-tricine-HYNIC-Tyr³-Octreotide was reported, and its details were also listed asfollows:1.Synthesis of bifunctional chelator agent—6-BOC-hydrazinopyridine-3-carboxylic acid (HYNIC (Boc))With 6-chloronicotinic acid as the original material, it was added to 80%hydrazine hydrate and placed in a l00℃ oil bath for 4 hrs, then hydrazinegroup was leaded into 6 position of pyridine to produce 6-hydrazinopyridine-3-carboxylic acid. After protecting the carboxylic acidwith tert-butyl carbonate, the desirable bifunctional chelator agent formed,which can be used to couple with peptides. The total yield of two stepswas 25%.2．Synthesis of HYNIC－Tyr³－Octreotide(HYNICTOC)The synthesis was performed in solution of NMP by coupling of 6－Boc- 中国原于能科学研究院硕士学位论文 上hydrazlnopyrldlne－3－c毗oxyllc acid(HYN－IC(Boo))to。－Lys'(Boo)－Tyr'－Octreotlde with the collpling reage血 HATU and dllsopropyethyl－amlne(DIPEA)as a base for removing water．The血ermedlate productwas deprotected to remove Boo protected－gro叩 using a mixture ofTM八hloanlsok／water (9／6／2) and山e crude produduct was purl丘ed onHPLC system．Pn门呵ICTOC was syh山eslzedln an over all yield of60％and apurlty of＞97％based on肝LC,then ltwas characterized bydetermlningthe exactmass on electronsprayaymass spectfoscopy3．Study for 99To"labelled HYNICTOCDiclne as a collgand,H'YNCTOC was吮elledby 99"n withusingthe"3＋I" ilXC＊lgapd aPWOSCh．SflQ2·H20 ＆S 8 fC讪Cts 血 sgCnt,HYNICTOC incubated with 99D"for 20mln In room tern－per�'�比,theradlochemlcal Purity was greater than 97％and the percent of 99n"－colhad less than％．4．Stu吟 of analytical methodThe method off且C and肝u was set叩协 analyzethe ingredle血s of"To"．colloid and"To"－tricine－HYNIC－Tyr'－Octreotlde．ITLC system［0．9％NaCI／Aceton(l／l),Rf"To＊－colloid二0．0－0．l；"To＊O。一,"To＊－(tricine)。and"To"－triclne－HYNICTOC－0．8－l．0］was used to analyze"To"－colloid；HPHPLC system［RP C－18 column,4．6x250mm,mobilephase:acetonltrlle／0亚％TFA solution,low rate刀mL／mln,the gra－ dieflt:0二％TFA,0－20min,90－0％2 20－22min,0－0％2 22－25min,0－90％225-30min, 90-90%1 can be aPplied to determine retefltion time (',Tc"O.-,Ret. Time 6.5min, ',Tc"-tficine-HYNICTOC, l l.5min).5.Study on biodistribution and imaging of 99Tcm-tricine-HYNICTOC withnude miceUsing the nude mice with pancreatic, breast, ovarian and colon carcinomaas animal model, biodistfiblltion of 99Tcm-tficine-HYNICTOC and its..imaging of y camera showed that the most radioactivity was excretedthrough urine; After 3hrs of injection, the ratio of Tumor/muscle wasgreater than 3.All of the above mentioned eXPeriments was carried out at the first timeof China, and the over all yield of synthesizing H'YNICTOC was 60%,which was maximum yield comparing to the present literature. All of theresults also suggested that HYNICTOC was a kind of promisingprecursor of 99Tcm 1abelled peptide in nuclear medicine.