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

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 68 Ga-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/cm 3 ). 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/cm 3 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/cm 3 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/cm 3 ( 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 68 Ga-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 177 Lu-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.