99mTc-Labeled Bombesin(7−14)NH2 with Favorable Properties for SPECT Imaging of Colon Cancer

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• 作者：Jiyun Shi ; Bing Jia ; Zhaofei Liu ; Zhi Yang ; Zilin Yu ; Kai Chen ; Xiaoyuan Chen ; Shuang Liu ; Fan Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：19
• 期：6
• 页码：1170 - 1178
• 全文大小：394K
• 年卷期：v.19,no.6(June 2008)
• ISSN：1520-4812

文摘

In this report, we present the synthesis and evaluation of the ^99mTc-labeled β-Ala-BN(7−14)NH₂ (ABN = β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂) as a new radiotracer for tumor imaging in the BALB/c nude mice bearing HT-29 human colon cancer xenografts. The gastrin releasing peptide receptor binding affinity of ABN and HYNIC-ABN (6-hydrazinonicotinamide) was assessed via a competitive displacement of ¹²⁵I-[Tyr4]BBN bound to the PC-3 human prostate carcinoma cells. The IC₅₀ values were calculated to be 24 2 nM and 38 1 nM for ABN and HYNIC-ABN, respectively. HYNIC is the bifunctional coupling agent for ^99mTc-labeling, while tricine and TPPTS (trisodium triphenylphosphine-3,3′,3′′-trisulfonate) are used as coligands to prepare the ternary ligand complex [^99mTc(HYNIC-ABN)(tricine)(TPPTS)] in very high yield and high specific activity. Because of its high hydrophilicity (log P = −2.39 0.06), [^99mTc(HYNIC-ABN)(tricine)(TPPS)] was excreted mainly through the renal route with little radioactivity accumulation in the liver, lungs, stomach, and gastrointestinal tract. The tumor uptake at 30 min postinjection (p.i.) was 1.59 0.23%ID/g with a steady tumor washout over the 4 h study period. As a result, it had the best T/B ratios in the blood (2.37 0.68), liver (1.69 0.41), and muscle (11.17 3.32) at 1 h p.i. Most of the injected radioactivity was found in the urine sample at 1 h p.i., and there was no intact [^99mTc(HYNIC-ABN)(tricine)(TPPTS)] detectable in the urine, kidney, and liver samples. Its metabolic instability may contribute to its rapid clearance from the liver, lungs, and stomach. Despite the steady radioactivity washout, the tumors could be clearly visualized in planar images of the BALB/c nude mice bearing the HT-29 human colon xenografts at 1 and 4 h p.i. The favorable excretion kinetics from the liver, lungs, stomach, and gastrointestinal tract makes [^99mTc(HYNIC-ABN)(tricine)(TPPTS)] a promising SPECT radiotracer for imaging colon cancer.