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

Abstract

Currently, 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). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, 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.

Authors:
 [1];  [2];  [2];  [3];  [2];  [2];  [2];  [4];  [2]
  1. Fudan Univ., Shanghai (China). Dept. of Nuclear Medicine; Stanford Univ., CA (United States). Molecular Imaging Program at Stanford (MIPS)
  2. Stanford Univ., CA (United States). Molecular Imaging Program at Stanford (MIPS)
  3. Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Radiation Oncology
  4. Fudan Univ., Shanghai (China). Dept. of Nuclear Medicine
Publication Date:
Research Org.:
Stanford Univ., CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1374983
Grant/Contract Number:  
SC0008397
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE

Citation Formats

Jiang, Lei, Tu, Yingfeng, Hu, Xiang, Bao, Ande, Chen, Hao, Ma, Xiaowei, Doyle, Tim, Shi, Hongcheng, and Cheng, Zhen. Pilot Study of 64Cu(I) for PET Imaging of Melanoma. United States: N. p., 2017. Web. doi:10.1038/s41598-017-02691-3.
Jiang, Lei, Tu, Yingfeng, Hu, Xiang, Bao, Ande, Chen, Hao, Ma, Xiaowei, Doyle, Tim, Shi, Hongcheng, & Cheng, Zhen. Pilot Study of 64Cu(I) for PET Imaging of Melanoma. United States. doi:10.1038/s41598-017-02691-3.
Jiang, Lei, Tu, Yingfeng, Hu, Xiang, Bao, Ande, Chen, Hao, Ma, Xiaowei, Doyle, Tim, Shi, Hongcheng, and Cheng, Zhen. Wed . "Pilot Study of 64Cu(I) for PET Imaging of Melanoma". United States. doi:10.1038/s41598-017-02691-3. https://www.osti.gov/servlets/purl/1374983.
@article{osti_1374983,
title = {Pilot Study of 64Cu(I) for PET Imaging of Melanoma},
author = {Jiang, Lei and Tu, Yingfeng and Hu, Xiang and Bao, Ande and Chen, Hao and Ma, Xiaowei and Doyle, Tim and Shi, Hongcheng and Cheng, Zhen},
abstractNote = {Currently, 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). But, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. In addition, 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.},
doi = {10.1038/s41598-017-02691-3},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {5}
}

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    Works referencing / citing this record:

    PET and SPECT imaging of melanoma: the state of the art
    journal, October 2017

    • Wei, Weijun; Ehlerding, Emily B.; Lan, Xiaoli
    • European Journal of Nuclear Medicine and Molecular Imaging, Vol. 45, Issue 1
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