Pre-therapeutic comparative dosimetry of 177Lu-rhPSMA-7.3 and 177Lu-PSMAI&T in patients with metastatic castration resistant prostate cancer (mCRPC).

Radiohybrid prostate-specific membrane antigen (rhPSMA)-ligands allow for labelling with 18F and radiometals for endoradiotherapy. rhPSMA-7.3 is designated as lead compound with promising preclinical data for 177Lu-rhPSMA-7. 3 indicating higher tumor uptake compared with 177Lu-PSMA-I&T. In this retrospective analysis we compared pre-therapeutic clinical dosimetry of both PSMA-ligands. Methods: Six mCRPC patients underwent both 177Lu-rhPSMA-7.3 and 177Lu-PSMA-I&T pre-therapeutic dosimetry. Whole-body scintigraphy was performed at 1h, 4h, 24h, 48h and 7d post injection. Regions of interest (ROI) covering the whole body, organs, bone marrow and tumor lesions per patient were drawn. Absorbed doses for individual patients and pre-therapeutic applications were calculated using OLINDA/EXM. To facilitate comparison of both ligands we introduced the therapeutic index (TI) defined as ratio of mean pre-therapeutic doses to tumor lesions over relevant organs-at-risk. Results: Mean whole-body pre-therapeutic effective doses were 0.12±0.07 vs. 0.05±0.03 Sv/GBq and mean absorbed organ doses were e.g. 1.65±0.28 vs. 0.73±0.18 Gy/GBq for the kidneys; 0.19±0.09 vs. 0.07±0.03 Gy/GBq for the liver and 2.35±0.78 vs. 0.80±0.41 Gy/GBq for the parotid, for the bone marrow 0.67±0.62 vs. 0.30±0.27 Gy/GBq for 177Lu-rhPSMA-7.3 vs. 177Lu-PSMA-I&T, respectively. Tumor lesions received a mean absorbed doses of 6.44±6.44 vs. 2.64±2.24 Gy/GBq for 177Lu-rhPSMA-7.3 vs. 177Lu-PSMA-I&T, respectively. The mean TI(kidney) and TI(bone_marrow) were 3.7±2.2 vs. 3.6±2.2 and 15.2±10.2 vs. 15.1±10.2, for 177Lu-rhPSMA-7.3 vs. 177Lu-PSMA-I&T, respectively. Conclusion: Pre-therapeutic clinical dosimetry confirmed preclinical results with 2-3 times higher mean absorbed doses for tumors of 177Lu-rhPSMA-7.3 compared to 177Lu-PSMA-I&T. Absorbed doses to normal organs also tended to be higher for 177Lu-rhPSMA-7.3 resulting overall in a similar average TI for both radiopharmaceuticals with considerable inter-patient variability. 177Lu-rhPSMA-7.3 holds promise for similar therapeutic efficacy as 177Lu-PSMA-I&T at lower amounts of injected activity simplifying radiation safety measurements (especially for large patient numbers and/or dose escalation regimes).

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2021 Sep 16 [Epub ahead of print]

Benedikt Feuerecker, Maythinee Chantadisai, Anne Allmann, Robert Tauber, Jakob Allmann, Lisa Steinhelfer, Isabel Rauscher, Alexander Wurzer, Hans-Jürgen Wester, Wolfgang Andreas Weber, Calogero D'Alessandria, Matthias Eiber

Klinikum rechts der Isar, Technical University of Munich, Germany., Chulalongkorn University, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society., Technical University of Munich., Klinikum rechts der Isar der Technischen Universität München., Technische Universitaet München., Klinikum rechts der Isar., Nuclear Medicine, TU Munich.