The tumour sink effect on 68Ga-PSMA-PET/CT in metastatic castration-resistant prostate cancer and its implications for PSMA-RPT: a sub-analysis of the 3TMPO study

Abstract

Background: The tumour sink effect is a phenomenon whereby the sequestration of a radiopharmaceutical in cancer lesions leads to decreased activity concentration in the blood stream and organs. The aim of this sub-analysis of the prospective 3TMPO study (NCT04000776) was to investigate the tumour sink effect on prostate-specific membrane antigen (PSMA) PET imaging in a population of patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Ninety-seven participants underwent 68Ga-PSMA-617 PET/CT imaging. The activity concentration in the kidney, parotid, spleen, liver and blood was expressed as a percentage of injected activity per cubic centimetre (%IA/cm3). The total tumour volume was delineated, and the total lesion fraction (TLF), i.e., the percentage of injected activity sequestered in the tumour, was computed. Participants were stratified into three tumour burden groups: small (TLF < 10%), moderate (10% ≤ TLF < 25%), and large (TLF ≥ 25%). Weight, lean body weight, body surface area, and estimated glomerular filtration rate (eGFR) were investigated as additional factors affecting biodistribution. Results: The TLF ranged from 0.0 to 43.5%. For all healthy tissues, the %IA/cm3 was negatively correlated with TLF (r ranging − 0.33 to − 0.46; P < 0.001). Patients with a large TLF had significantly lower uptake in all organs when compared to those with a small TLF (P < 0.05). Body habitus indices and/or eGFR were negatively correlated with the %IA/cm3 of the parotid, liver and blood (r ranging − 0.23 to − 0.33; P < 0.05). Combining predictive variables, the term [BSA / (1–TLF)] tended to yield the strongest negative correlations with healthy tissues %IA/cm3 (r ranging − 0.33 to − 0.63; P < 0.001). Conclusion: The tumour sink effect was observed in a cohort of mCRPC patients scanned with 68Ga-PSMA-617. This finding strongly suggests that patients with a large TLF are likely to receive lower absorbed doses to organs at risk – i.e., be undertreated from a dosimetry perspective – following a fixed-activity regime of 177Lu-PSMA-617 radiopharmaceutical therapy, as commonly practiced. Individual factors such as body habitus and renal function further impact the biodistribution of PSMA radiopharmaceuticals. Trial registration: NCT04000776, registered on 2019-06-27.