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Objective:  To investigate the therapeutic efficacy of intratumoral injection of  125 I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by  99m Tc-HYNIC-duramycin and  99m Tc-HYNIC-3PRGD2 SPECT/CT imaging.   Methods:  HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (μCi)  125 I-AA98 mAb, free  125 I, AA98 mAb, 80 μCi  125 I-AA98 mAb, and 200 μCi  125 I-AA98 mAb.  99m Tc-HYNIC-duramycin and  99m Tc-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  99m Tc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 μCi group, 10 μCi group and free  125 I group on day 3, respectively (all  P  < 0.05). On day 3, there was a markedly positive correlation between T/M ratio from  99m Tc-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  99m Tc-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 α ν β 3  staining ( P  > 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 μCi, 80 μCi, free  125 I, and 200 μCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively.   Conclusion:   125 I-AA98 mAb showed more effective apoptosis induced ability for CD146 high expression Hep G2 HCC cells and hold the potential for HCC treatment. Moreover,  99m Tc-HYNIC-Duramycin (apoptosis-targeted) imaging and  99m Tc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.

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