Biokinetic and dosimetric aspects of ⁶⁴CuCl₂ in human prostate cancer: possible theranostic implications

The aim of the present study is to evaluate the kinetics and dosimetry of ⁶⁴CuCl₂ in human prostate cancer (PCa) lesions. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external beam radiation therapy. All patients underwent ⁶⁴CuCl₂-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each ⁶⁴CuCl₂ avid PCa lesion with a diameter > 1 cm on mpMRI in each patient. Time-activity curves for all lesions were obtained. The effective and biological half-life and the standard uptake values (SUVs) were calculated. Tumour/background ratio (TBR) curves as a function of time were considered. Finally, the absorbed dose per lesion was estimated.

The mean effective half-life of ⁶⁴CuCl₂ calculated in the lymph nodes (10.2 ± 1.7 h) was significantly higher than in local relapses (8.8 ± 1.1 h) and similar to that seen in bone metastases (9.0 ± 0.4 h). The mean ⁶⁴CuCl₂ SUV_max calculated 1 h after tracer injection was significantly higher in the lymph nodes (6.8 ± 4.3) and bone metastases (6.8 ± 2.9) than in local relapses (4.7 ± 2.4). TBR mean curve of ⁶⁴CuCl₂ revealed that the calculated TBR_max value was 5.0, 7.0, and 6.2 in local relapse and lymph node and bone metastases, respectively, and it was achieved about 1 h after ⁶⁴CuCl₂ injection. The mean absorbed dose of the PCa lesions per administrated activity was 6.00E-2 ± 4.74E-2mGy/MBq. Indeed, for an administered activity of 3.7 GBq, the mean dose absorbed by the lesion would be 0.22 Gy.

Dosimetry showed that the dose absorbed by PCa recurrences/metastases per administrated activity was low. The dosimetric study performed does not take into account the possible therapeutic effect of the Auger electrons. Clinical trials are needed to evaluate ⁶⁴Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.