Pretherapeutic Comparative Dosimetry of 177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer

Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands allow for labeling with F-18 and radiometals for endoradiotherapy. rhPSMA-7.3 has been designated as a lead compound with promising preclinical data for Lu-177-rhPSMA-7.3, which has shown higher tumor uptake than Lu-177-PSMA I&T. In this retrospective analysis, we compared pretherapeutic clinical dosimetry data of both PSMA ligands. Methods: Six patients with metastatic castration-resistant prostate cancer underwent both Lu-177-rhPSMA-7.3 and Lu-177-PSMA I&T pretherapeutic dosimetry. Whole-body scintigraphy was performed at 1 h, 4 h, 24 h, 48 h, and 7 d after injection. Regions of interest covering the whole body, organs, bone marrow, and tumor lesions were drawn for each patient. Absorbed doses for individual patients and pretherapeutic applications were calculated using OLINDA/EXM. To facilitate the comparison of both ligands, we introduced the therapeutic index (TI), defined as the ratio of mean pretherapeutic doses to tumor lesions over relevant organs at risk. Results: Mean whole-body pretherapeutic effective doses for Lu-177-rhPSMA-7.3 and Lu-177-PSMA I&T were 0.12 +/- 0.07 and 0.05 +/- 0.03 Sv/GBq, respectively. Mean absorbed organ doses for Lu-177-rhPSMA-7.3 and Lu-177-PSMA I&T were, for example, 1.65 +/- 0.28 and 0.73 +/- 0.18 Gy/GBq for the kidneys, 0.19 +/- 0.09 and 0.07 +/- 0.03 Gy/GBq for the liver, 2.35 +/- 0.78 and 0.80 +/- 0.41 Gy/GBq for the parotid gland, and 0.67 +/- 0.62 and 0.30 +/- 0.27 Gy/GBq for the bone marrow, respectively. Tumor lesions received mean absorbed doses of Lu-177-rhPSMA-7.3 and Lu-177-PSMA I&T of 6.44 +/- 6.44 and 2.64 +/- 2.24 Gy/GBq, respectively. The mean TIs for the kidneys were 3.7 +/- 2.2 and 3.6 +/- 2.2 for Lu-177-rhPSMA-7.3 and Lu-177-PSMA I&T, respectively, and those for the bonemarrowwere 15.2 +/- 10.2 and 15.1 +/- 10.2 for Lu-177-rhPSMA-7.3 and (17)7Lu-PSMA I&T, respectively. Conclusion: Pretherapeutic clinical dosimetry confirmed preclinical results of mean absorbed doses for tumors that were 2-3 times higher for Lu-177-rhPSMA-7.3 than for Lu-177-PSMA I& T. Absorbed doses to normal organs also tended to be higher for Lu-177-rhPSMA-7.3, resulting overall in similar average TIs for both radiopharmaceuticals with considerable interpatient variability. Lu-177-rhPSMA-7.3 has promise for a therapeutic efficacy similar to that of Lu-177-PSMA I&T at smaller amounts of injected activity, simplifying radiation safety measurements (especially for large patient numbers or dose escalation regimens).