[⁶⁴Cu]CuCl₂ as a Novel Metabolic Marker of Progression and Survival in Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (miBC) is an aggressive malignancy that can be visualised with [⁶⁴Cu]Copper-dichloride ([⁶⁴Cu]CuCl₂) PET/CT, due to the increased copper avidity of this cancer. Moreover, [⁶⁴Cu]CuCl₂ could also show a predictive role in patients undergoing platinum-based chemotherapy, since both metals enter the cell via the same transporter, CTR-1. In this study, we tested the prognostic and predictive power of [⁶⁴Cu]CuCl₂ PET/CT in miBC.

Patients with available [⁶⁴Cu]CuCl₂ PET/CT images and follow-up data were included in the study. Volumes-of-interest (VOIs) were drawn on the primary tumour, nodal metastases, and distant metastases; their sum was defined as the whole-body tumour volume. From these VOIs, SUVmax, SUVmean, SUVmin, Volume, and total lesion copper uptake (TLC) were extracted. These parameters were compared with progression-free survival (PFS), disease-specific survival (DSS) and chemotherapy response.

Thirty patients (six women) were included. SUVmean of the primary (p < 0.05), as well as its SUVmax, volume, and TLC (p < 0.01), were higher in patients with disease progression and in those who died of disease. Whole-body tumour volume (p = 0.001) and the presence of metastases (p = 0.024) were independent predictors of PFS; whole-body tumour volume was the only parameter with borderline significance in the DSS model (p = 0.067). Patients progressing under chemotherapy had a higher whole-body tumour volume and TLC (p < 0.05) than those who didn't.

[⁶⁴Cu]CuCl₂ can assess the presence of miBC within the bladder and at remote localisations, providing an accurate estimate of the disease burden at the time of examination, which, in turn, enables prognostic assessment in these patients. Moreover, rather than being a predictor of platinum-based chemotherapy effectiveness, copper uptake signals tumour aggressiveness and resistance to this systemic treatment.