Theranostics of Malignant Melanoma with ⁶⁴CuCl₂

Abstract

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.