title: 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 (64)CuCl2 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 (64)CuCl2. 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 (64)CuCl2. Dynamic scans were also obtained for B16F10 tumor-bearing mice. All mice were sacrificed at 72 h after injection of (64)CuCl2, and biodistribution studies were performed. Mice bearing B16F10 or A375M tumors were further subjected to (64)CuCl2 radionuclide therapy. Specifically, when the tumor size reached 0.5-0.8 cm in diameter, tumor-bearing mice were systemically administered (64)CuCl2 (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). (64)CuCl2 displayed high and specific uptake in B16F10 and A375M cells. In vivo (64)CuCl2 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 (64)CuCl2 treatment were much slower than that of the control group.
  
  
  CONCLUSIONS
  Both melanotic and amelanotic melanomas (B16F10 and A375M) tested were found to overexpress CTR1. The tumors can be successfully visualized by (64)CuCl2 PET and further treated by (64)CuCl2, highlighting the high potential of using (64)CuCl2 as a theranostic agent for the management of melanoma.
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, Stanford, California; and.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qin
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Lan
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D003301:Copper Radioisotopes; D000079923:Copper Transporter 1; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D027682:Cation Transport Proteins; D003301:Copper Radioisotopes; D000079923:Copper Transporter 1; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C490079:SLC31A1 protein, human; D003300:Copper; C029892:cupric chloride
keywords: 64CuCl2; PET; copper transporter 1; melanoma; radionuclide therapy