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

Abstract

The goal of this study is to evaluate a new (18) F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new (18) F-labeled imaging agent [(18) F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with (18) F using NOTA-AlF chelation method. The tumor-targeting characteristics of [(18) F]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 [(18) F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [(18) F]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 [(18) F]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, [(18) F]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, [(18) F]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 © 2016 John Wiley & Sons, Ltd.