AUTHOR=Zhou Jun , Hu Pengcheng , Si Zhan , Tan Hui , Qiu Lin , Zhang He , Fu Zhequan , Mao Wujian , Cheng Dengfeng , Shi Hongcheng 

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

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2019.00319

DOI=10.3389/fbioe.2019.00319

ISSN=2296-4185

ABSTRACT=<p><bold>Objective:</bold> To investigate the therapeutic efficacy of intratumoral injection of <sup>125</sup>I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by <sup>99m</sup>Tc-HYNIC-duramycin and <sup>99m</sup>Tc-HYNIC-3PRGD2 SPECT/CT imaging.</p><p><bold>Methods:</bold> HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (μCi) <sup>125</sup>I-AA98 mAb, free <sup>125</sup>I, AA98 mAb, 80 μCi <sup>125</sup>I-AA98 mAb, and 200 μCi <sup>125</sup>I-AA98 mAb. <sup>99m</sup>Tc-HYNIC-duramycin and <sup>99m</sup>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.</p><p><bold>Results:</bold> In terms of apoptosis, the 200 μCi group demonstrated the highest apoptotic index (11.8 ± 3.8%), and its T/M ratio achieved by <sup>99m</sup>Tc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 μCi group, 10 μCi group and free <sup>125</sup>I group on day 3, respectively (all <italic>P</italic> &lt; 0.05). On day 3, there was a markedly positive correlation between T/M ratio from <sup>99m</sup>Tc-HYNIC-duramycin imaging and apoptotic index by TUNEL staining (<italic>r</italic> = 0.6981; <italic>P</italic> &lt; 0.05). Moreover, the 200 μCi group showed the lowest T/M ratio on <sup>99m</sup>Tc-HYNIC-3PRGD2 imaging (1.0 ± 0.5) on day 7 (all <italic>P</italic> &lt; 0.05) comparing to other groups. The T/M ratio on day 7 was not correlated with integrin α<sub>ν</sub>β<sub>3</sub> staining (<italic>P</italic> &gt; 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 μCi, 80 μCi, free <sup>125</sup>I, and 200 μCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively.</p><p><bold>Conclusion:</bold><sup>125</sup>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, <sup>99m</sup>Tc-HYNIC-Duramycin (apoptosis-targeted) imaging and <sup>99m</sup>Tc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.</p>