Pilot Study of 64Cu(I) for PET Imaging of Melanoma

Sci Rep. 2017 May 31;7(1):2574. doi: 10.1038/s41598-017-02691-3.

Abstract

At present, 64Cu(II) labeled tracers including 64CuCl2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Compared with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). However, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. Additionally, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / genetics
  • Cell Line, Tumor
  • Copper Radioisotopes / chemistry
  • Copper Radioisotopes / pharmacology*
  • Copper Transporter 1
  • Humans
  • Melanoma / diagnostic imaging*
  • Melanoma / pathology
  • Mice
  • Molecular Imaging / methods*
  • Pilot Projects
  • Positron-Emission Tomography / methods*
  • Tissue Distribution

Substances

  • Cation Transport Proteins
  • Copper Radioisotopes
  • Copper Transporter 1
  • Copper-64