Dosimetry Estimate and Initial Clinical Experience with 90 Y-PSMA-617

Because of different physical properties, the β-emitters Lu and Y offer specific radiologic-biologic advantages in dedicated clinical situations. Our objective was to introduce Y-labeled prostate-specific membrane antigen (PSMA)-617 to clinical application, providing additional avenues for personalized medicine. Here, we present our dosimetry estimate for Y-PSMA-617, report first clinical experiences, and discuss the advantages and drawbacks of varying the β-emitter in PSMA-targeting radioligand therapy. To approximate radiation dosimetry, 4 patients with metastatic castration-resistant prostate cancer underwent serially performed imaging up to 1 wk after Lu-PSMA-617 therapy. Time-activity curves were extrapolated to the half-life of Y, and OLINDA was used to calculate the dosimetry estimate. In clinical practice, 11 patients with PSMA-positive lymph-nodal bulk disease were stratified to receive Y-PSMA-617 radioligand therapy (mean, 3.2 GBq; range, 2.8-3.7 GBq); afterward, safety lab tests, prostate-specific antigen (PSA) response, and clinical findings were thoroughly followed. The projected dosimetry for Y-PSMA-617 estimated a mean kidney dose of 3.47 ± 1.40 Gy/GBq, red marrow dose of 0.11 ± 0.04 Gy/GBq, and salivary gland dose of 5.57 ± 1.34 Gy/GBq; randomly chosen metastases were approximated with 22.8 ± 16.10 Gy/GBq. The observed acute hematologic toxicity (5 cases of leukopenia and 2 of thrombocytopenia, all grade 1 or 2) and clinical side effects (2 cases of transient xerostomia and 1 of nausea, all grade 1 or 2), as well as PSA response (any PSA response, 7/11 patients; >50% PSA decline, 5/11 patients), were comparable to Lu-PSMA-617 literature data. A factor 3-4 lower treatment activity for Y-PSMA-617 translates into a comparable dosimetry estimate and clinical findings similar to those of Lu-PSMA-617. However, safety was demonstrated only for patients with oligometastatic disease. Further studies are needed to evaluate its potential in patients with more disseminated bone involvement or visceral metastasis.