Tracer kinetics in dual time-point ¹⁷⁷ Lu-PSMA post-therapy SPECT/CT scan predicts treatment outcome in prostate cancer patients

Ziel/Aim ¹⁷⁷Lu-PSMA ligand radiotherapy (PLRT) leads to clinical response in a large percentage of metastasized castration-resistant prostate cancer (mCRPC) patients. However, some patients do progress in the course of PLRT, in spite of intensive tumor uptake in pre-therapeutic PSMA-PET/CT. Retention kinetic of the radiopharmaceutical within tumor lesions might play a relevant role determining the absorbed dose. In this study, we analyzed the changes in radioactivity concentration between two post-PLRT scans and compared this information with the therapy outcome.

Methodik/Methods 91 mCRPC patients (mean age 71±9 years) were retrospectively enrolled. All patients had undergone at least two ¹⁷⁷Lu-PSMA cycles. For each patient, a representative lesion (RL) with the highest uptake and a volume of a least 5 ml was selected and defined on the pre-therapy PSMA-PET/CT, using an isocontour method (41 % of SUV_max); RL SUV was determined. Target-to-background ratio (TBR) of RL was then calculated on the two SPECT/CT performed one and two days after the first PLRT, by dividing the mean RL counting rate by the one of the vena cava blood pool. Response to PRLT was defined as at least 50 % PSA drop after two cycles.

Ergebnisse/Results Fifty-five patients (59 %) were classified as responders. In these patients, mean RL TBR increased by 34±19 % from the first to the second day after PLRT. Conversely, non-responders showed a significantly smaller mean TBR increase (5 ± 9 %, p = 0,016). Mean TBR increase showed a direct correlation with PSA decrease after two ¹⁷⁷Lu-PSMA cycles (R = 0,63; p < 0,001). Mean SUV, mean baseline PSA, and absolute TBR values were not significantly different between responders and non-responders.

Schlussfolgerungen/Conclusions Effectiveness of the ¹⁷⁷Lu-PSMA seems to be related to the intratherapeutic radiopharmaceutical kinetic, rather than to the absolute uptake value. Increasing uptake values between the first and second day after ¹⁷⁷Lu-PSMA administration suggest longer biological half-life within lesions, possibly purporting a higher tumor irradiation dose.