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

Abstract

Background: 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.

Results: 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.

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 ⁶⁴Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.

Keywords: 64CuCl2; Elderly; Kinetics and dosimetry; Prostate cancer; Theranostic.

Fig. 1

PVE corrected time-activity curves of ⁶⁴CuCl₂ (as a percentage of injected activity/mL) for the three different site of disease: local (a), lymph node (b) and bone (c) (in red the mean curves)

Fig. 2

An 85-year-old man affected by Gleason 4+3 PCa treated with EBRT, with rising PSA level (6.0 ng/mL) and PSA doubling time of 15 months. ⁶⁴CuCl₂-PET/CT images (axial and MIP) revealed focal and pathologic tracer uptake (arrows) in correspondence to the prostate apex close to the midline 1 h after the injection (a). An important reduction of tracer uptake was observed 4 (b) and 24 h (c) after the injection. Maximum intensity projection (d) visualized the differences in terms of uptake between the organsand prostate relapse

Fig. 3

Box plot representation of PVE corrected SUV_mean and SUV_max values 1 h after tracer injection, the effective half-life, the time-integrated activity coefficient and the absorbed dose (per administrated activity) for the three sites of disease

Fig. 4

Specific concentration (as a percentage of injected activity) for lesions (for each site of disease) and the main organs at risk 1, 4 and 24 h after administration

Fig. 5

⁶⁴CuCl₂ TBR curves over the time for the three different site of disease: local (a), lymph node (b) and bone (c) (in red the mean curves)

Fig. 6

Absorbed dose per administrated activity in PCa lesions (for each site of disease), red marrow, pancreas, kidneys and liver