Evaluation of non-small cell lung cancer by PET/CT with ⁶⁴CuCl₂: initial experience in humans

Human copper transporter 1 (hCtr1) is the main transporter of copper which has been involved as an essential cofactor in biological processes and mechanisms of action for cisplatin and its analogues. Although expression of hCtr1 is present in all tissues that require copper, several studies have showed that levels of expression are highly variable between normal and neoplastic tissues. We evaluated the potential diagnostic of the ⁶⁴CuCl₂-PET/CT in patients with wild type non-small cell lung cancer (NSCLC). Eleven patients were included. Baseline ¹⁸F-FDG-PET/CT and ⁶⁴CuCl₂-PET/CT performed before to initiate treatment with platinum-based chemotherapy. ¹⁸F-FDG-PET/CT detected a total of 68 lesions in different corporal sites: lung (24), regional lymph node (30), distant non-bone metastases (17) and bone metastases (14). Of total, 73% demonstrated high focal uptake of ⁶⁴CuCl₂-PET/CT: 36% in primary tumor and 27% in lymph-nodes metastases. The detection-rates (DRs) was lower with ⁶⁴CuCl₂ PET/CT compared to ¹⁸F-FDG-PET/CT, however, these was not statistically significant (P = 0.108). A complete match was found in 2 patients. All patients were treated with platinum-based chemotherapy. According to RECIST 1.1 and PERCIST 1.0 criteria, most patients with highest uptake ⁶⁴CuCl₂-PET/CT presented partial response (mean 3 cycles) corroborated with ¹⁸F-FDG PET/CT. On the other hand, patients with very low uptake or faint uptake have progressive disease (3/16 patients). To our knowledge, this is the first study with ⁶⁴CuCl₂-PET/CT in-human in patients with NSCLC chemo-naïve. Our results may represent that ⁶⁴CuCl₂-PET/CT had a good ability for detect lesions. In addition, the ⁶⁴CuCl₂ uptake is based on the expression of Ctr1 transporters seeking to differentiate between those patients who may benefit from platinum-based therapy. More studies are necessary for confirm these findings.