Treatment of Hepatocellular Carcinoma by Intratumoral Injection of 125I-AA98 mAb and Its Efficacy Assessments by Molecular Imaging.

Objective: To investigate the therapeutic efficacy of intratumoral injection of 125I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by 99mTc-HYNIC-duramycin and 99mTc-HYNIC-3PRGD2 SPECT/CT imaging. Methods: HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (µCi) 125I-AA98 mAb, free 125I, AA98 mAb, 80 µCi 125I-AA98 mAb, and 200 µCi 125I-AA98 mAb. 99mTc-HYNIC-duramycin and 99mTc-HYNIC-3PRGD2 micro-SPECT/CT imaging were performed on days 3 and 7, respectively. The T/M ratio for each imaging was compared with the corresponding immunohistochemical staining at each time point. The relative tumor inhibition rates were documented. Results: In terms of apoptosis, the 200 µCi group demonstrated the highest apoptotic index (11.8 ± 3.8%), and its T/M ratio achieved by 99mTc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 µCi group, 10 µCi group and free 125I group on day 3, respectively (all P < 0.05). On day 3, there was a markedly positive correlation between T/M ratio from 99mTc-HYNIC-duramycin imaging and apoptotic index by TUNEL staining (r = 0.6981; P < 0.05). Moreover, the 200 µCi group showed the lowest T/M ratio on 99mTc-HYNIC-3PRGD2 imaging (1.0 ± 0.5) on day 7 (all P < 0.05) comparing to other groups. The T/M ratio on day 7 was not correlated with integrin ανß3 staining (P > 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 µCi, 80 µCi, free 125I, and 200 µCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively. Conclusion: 125I-AA98 mAb showed more effective apoptosis induced ability for CD146 high expression Hep G2 HCC cells and hold the potential for HCC treatment. Moreover, 99mTc-HYNIC-Duramycin (apoptosis-targeted) imaging and 99mTc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.