Novel Radiolabeled TMTP1 for Long-Acting Hepatocellular Carcinoma Therapeutics.

Currently, the 5-year survival rate for patients with advanced hepatocellular carcinoma (HCC) is very low. Therefore, there is an urgent need to find new strategies for the treatment of HCC. TMTP1 (NVVRQ) is a tumor-homing peptide that has been shown to target a range of highly metastatic tumor cells. In this study, a novel radiotherapeutic probe, [Lu]Lu-DOTA-EB-TMTP1, was synthesized and used to explore the antitumor efficacy in an HCC tumor model. The albumin-binding TMTP1 radioligand was achieved with >98% radiochemical purity. Long tumor retention property of [Lu]Lu-DOTA-EB-TMTP1 was exhibited in single photon emission computed tomography (SPECT) imaging and biodistribution study. The [Lu]Lu-DOTA-EB-TMTP1 showed significant accumulation in the SMMC-7721 HCC tumor with an uptake value of 9.67 ± 1.27 %ID/g at 8 h and a T/M ratio of 6.4. In radiotherapy studies, 30 days after injection of [Lu]Lu-DOTA-EB-TMTP1, the tumor inhibition rate reached 93.2 ± 0.10 and 94.9 ± 0.04% in the 18.5 and 29.6 MBq high-dose groups, respectively. These preclinical data suggest that [Lu]Lu-DOTA-EB-TMTP1 may be an effective treatment option for HCC and should be further evaluated in human trials.