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

Background: The aim of the present study is to evaluate the kinetics and dosimetry of (CuCl2)-Cu-64 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 (CuCl2)-Cu-64-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each (CuCl2)-Cu-64 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. Results: The mean effective half-life of (CuCl2)-Cu-64 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 (CuCl2)-Cu-64 SUVmax 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 (CuCl2)-Cu-64 revealed that the calculated TBRmax 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 (CuCl2)-Cu-64 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. Conclusions: 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 Cu-64 internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.