RT Journal Article
SR Electronic
T1 Theranostics of Malignant Melanoma with <sup>64</sup>CuCl<sub>2</sub>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.113.133850
DO 10.2967/jnumed.113.133850
A1 Qin, Chunxia
A1 Liu, Hongguang
A1 Chen, Kai
A1 Hu, Xiang
A1 Ma, Xiaowei
A1 Lan, Xiaoli
A1 Zhang, Yongxue
A1 Cheng, Zhen
YR 2014
UL http://jnm.snmjournals.org/content/early/2014/03/12/jnumed.113.133850.abstract
AB Human copper transporter 1 (CTR1) is overexpressed in a variety of cancers. This study aimed to evaluate the use of 64CuCl2 as a theranostic agent for PET and radionuclide therapy of malignant melanoma. Methods: CTR1 expression levels were detected by Western blot analysis of a group of tumor cell lines. Two melanoma cell lines (B16F10 and A375M) that highly expressed CTR1 were then selected to study the uptake and efflux of 64CuCl2. Mice bearing B16F10 or A375M tumors (n = 4 for each group) were subjected to 5 min of static whole-body PET scans at different time points after intravenous injection of 64CuCl2. Dynamic scans were also obtained for B16F10 tumor–bearing mice. All mice were sacrificed at 72 h after injection of 64CuCl2, and biodistribution studies were performed. Mice bearing B16F10 or A375M tumors were further subjected to 64CuCl2 radionuclide therapy. Specifically, when the tumor size reached 0.5–0.8 cm in diameter, tumor-bearing mice were systemically administered 64CuCl2 (∼74 MBq) or phosphate-buffered saline, and tumor sizes were monitored over the treatment period. Results: CTR1 was found to be overexpressed in the cancer cell lines tested at different levels, and high expression levels in melanoma cells and tissues were observed (melanotic B16F10 and amelanotic A375M). 64CuCl2 displayed high and specific uptake in B16F10 and A375M cells. In vivo 64CuCl2 PET imaging demonstrated that both B16F10 and A375M tumors were clearly visualized. Radionuclide treatment studies showed that the tumor growth in both the B16F10 and the A375M models under 64CuCl2 treatment were much slower than that of the control group. Conclusion: Both melanotic and amelanotic melanomas (B16F10 and A375M) tested were found to overexpress CTR1. The tumors can be successfully visualized by 64CuCl2 PET and further treated by 64CuCl2, highlighting the high potential of using 64CuCl2 as a theranostic agent for the management of melanoma.