Syntheses and preliminary evaluation of [18F]AlF-NOTA-G-TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

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• 作者：Yesen Li ; Deliang Zhang ; Ying Shi ; Zhide Guo ; Xinying Wu ; Jian-Lin Ren ; Xianzhong Zhang and Hua Wu
• 刊名：Contrast Media & Molecular Imaging
• 出版年：2016
• 出版时间：July/August 2016
• 年：2016
• 卷：11
• 期：4
• 页码：262-271
• 全文大小：619K
• ISSN：1555-4317

文摘

The goal of this study is to evaluate a new ¹⁸F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new ¹⁸F-labeled imaging agent [¹⁸F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with ¹⁸F using NOTA-AlF chelation method. The tumor-targeting characteristics of [¹⁸F]AlF-NOTA-G-TMTP1 was assessed in HepG2, SMCC-7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1–14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C₁₈ column. The log P value of [¹⁸F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [¹⁸F]AlF-NOTA-G-TMTP1 accumulated in SMCC-7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post-injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [¹⁸F]AlF-NOTA-G-TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G-TMTP1 in SMCC-7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [¹⁸F]AlF-NOTA-G-TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [¹⁸F]AlF-NOTA-G-TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright