PT  - JOURNAL ARTICLE
AU  - Kim, Kwang Il
AU  - Jang, Su Jin
AU  - Park, Ju Hui
AU  - Lee, Yong Jin
AU  - Lee, Tae Sup
AU  - Woo, Kwang Sun
AU  - Park, Hyun
AU  - Choe, Jae Gol
AU  - An, Gwang Il
AU  - Kang, Joo Hyun
TI  - Detection of Increased <sup>64</sup>Cu Uptake by Human Copper Transporter 1 Gene Overexpression Using PET with <sup>64</sup>CuCl<sub>2</sub> in Human Breast Cancer Xenograft Model
AID  - 10.2967/jnumed.114.141127
DP  - 2014 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1692--1698
VI  - 55
IP  - 10
4099  - http://jnm.snmjournals.org/content/55/10/1692.short
4100  - http://jnm.snmjournals.org/content/55/10/1692.full
SO  - J Nucl Med2014 Oct 01; 55
AB  - Copper is an essential cofactor for a variety of biochemical processes including oxidative phosphorylation, cellular antioxidant activity, and elimination of free radicals. The copper transporter 1 is known to be involved in cellular uptake of copper ions. In this study, we evaluated the utility of human copper transporter 1 (hCTR1) gene as a new reporter gene for 64Cu PET imaging. Methods: Human breast cancer cells (MDA-MB-231) were infected with a lentiviral vector constitutively expressing the hCTR1 gene under super cytomegalovirus promoter, and positive clones (MDA-MB-231-hCTR1) were selected. The expression of hCTR1 gene in MDA-MB-231-hCTR1 cells was measured by reverse transcription polymerase chain reaction, Western blot, and 64Cu uptake assay. To evaluate the cytotoxic effects induced by hCTR1 expression, the dose-dependent cell survival rate after treatment with cisplatin (Cis-diaminedichloroplatinum (II) [CDDP]) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion. Small-animal PET images were acquired in tumor-bearing mice from 2 to 48 h after an intravenous injection of 64Cu. Results: The hCTR1 gene expression in MDA-MB-231-hCTR1 cells was confirmed at the RNA and protein expression and the cellular 64Cu uptake level. MTT assay and trypan blue dye exclusion showed that the cell viability of MDA-MB-231-hCTR1 cells decreased more rapidly than that of MDA-MB-231 cells after treatment with CDDP for 96 or 72 h, respectively. Small-animal PET imaging revealed a higher accumulation of 64Cu in MDA-MB-231-hCTR1 tumors than in MDA-MB-231 tumors. With respect to the biodistribution data, the percentage injected dose per gram of 64Cu in the MDA-MB-231 tumors and MDA-MB-231-hCTR1 tumors at 48 h after 64Cu injection was 2.581 ± 0.254 and 5.373 ± 1.098, respectively. Conclusion: An increase in 64Cu uptake induced by the expression of hCTR1 gene was demonstrated in vivo and in vitro, suggesting the potential use of hCTR1 gene as a new imaging reporter gene for PET with 64CuCl2.