99Tcm-（HYNIC-[Lys3]-BBS）（tricine）（tricine）的制备及对胰腺癌荷瘤鼠显像研究

目的制备99Tcm-（联肼尼克酰胺-蛙皮素类似肽）（N-三羟甲基甘氨酸）（三苯基膦三间磺酸钠盐）（HYNIC-Lys3]-BBS）（tricine）（TPPTS）]三重配位化合物，评价其在正常小鼠及胰腺癌荷瘤裸小鼠的生物分布。方法双功能螯合剂HYNIC与Lys3]-BBS偶联（pH值9．0），以SnCl2为还原剂，tricine和TPPTS为协同配体，进行99Tcm-标记，合成三重配位化合物99Tcm-（HYNIC-Lys。]-BBS）（tricine）（TPPTS）。用Sep-PakC18cartridge和HPLC对其纯化和分析，测定其标记率和放化纯，研究其在人血清中的稳定性，并进行正常小鼠体内的生物分布研究以及胰腺癌荷瘤裸小鼠活体显像。结果99Tcm-（HYNIC_Lys3]-BBS）（tricine）（TPPTS）标记率为（90±2）％，放化纯〉95％，在人血清中放置4h其放化纯仍大于85％。正常小鼠体内分布结果表明，99Tcm-（HYNIC-Lys3]-BBS）（tricine）（TPPTS）血液清除迅速，2h血液中放射性为（0．07±0．01）％ID／g，主要经。肾排泄，肝、胃肠道摄取较少，2h时肝放射性为（0．27±0．03）％ID／g，胃为（0．06±0．03）％ID／g，肠为（0．04±0．00）％ID／g。胰腺癌荷瘤裸小鼠吖显像可见肿瘤部位有放射性浓聚影，2h后肿瘤与对侧正常肌肉的T／NT比值最高达3．71±0．57。结论99Tcm-（HYNIC-Lys3]-BBS）（tricine）（TPPTS）三重配位化合物制备成功，所用标记方法可行，标记物稳定性较好，标记率和放化纯较高，生物分布特性良好，有望用于胰腺癌的显像研究。

Preparation and evaluation of 99Tcm-(HYNIC-[Lys3] -bombesin) (tricine) (TPPTS) for imaging the Balb/c nude mice bearing human pancreatic cancer

Objective To synthesize 99Tcm- (hydrazinonictinamide- Lys3] -bombesin) (tricine)(trisodium triphenylphosphine-3,3',3"-trisulfonate) ((HYNIC-Lys3]-BBS) (tricine) (TPPTS)) and evaluate its biodistribution and binding capability with tumor tissue in Balb/c nude mice bearing human pancreatic cancer xenografts. Methods HYNIC was conjugated to the Lys3] -BBS at pH = 9.0 with SnCl2 as reducing agent and both tricine and TPPTS as coligands for 99Tcm-labeling. 99Tcm-HYNIC-Lys3]-BBS)(tricine) (TPPTS) was purified by Sep-Pak C18 cartridge and was analysed by HPLC. The radiochemical purity and radiolabeling yield were measured. The stability of 99Tcm-(HYNIC-Lys3]-BBS) (tricine)(TPPTS) in serum, biodistribution (% ID/g) in the normal mice and imaging of the Balb/c nude mice bearing human pancreatic cancer xenografts in vivo were studied. Results The radiolabeling yield was (90 ±2)% and the radiochemical purity was over 95%. The radiochemical purity after 4 h in serum was over 85%. The distribution in normal mice showed rapid clearance from blood (the uptake was (0.07 ±0.01) %ID/g at 2 h postinjection). 99Tcm-(HYNIC-Lys3]-BBS) (tricine) (TPPTS) was excreted mainly via the kidney with little radioactivity accumulation in the liver and gastrointestinal tract (the uptake of liver, stomach, intestine was (0.27 ±0.03), (0.06 ±0.03), (0.04 ±0.00) %ID/g at 2 h postinjection). Marked uptake of radioactivity was found in tumor tissue of the Balb/c nude mice bearing human pancreatic cancer with maximum T/NT ratio of 3.71 ± 0.57 at 2 h postinjection. Conclusions 99Tcm-(HYNIC-Lys3]-BBS)(tricine) (TPPTS) can be easily prepared with high radiolabeling yield and radiochemical purity. The stability in serum and good biodistribution charateristics make it useful for the diagnosis of human pancreatic cancer with over-expression of the gastric-releasing peptide(GRP) receptor.