RT Journal Article SR Electronic T1 Dosimetry Estimate and Initial Clinical Experience with 90Y-PSMA-617 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 806 OP 811 DO 10.2967/jnumed.118.218917 VO 60 IS 6 A1 Hendrik Rathke A1 Paul Flechsig A1 Walter Mier A1 Marcus Bronzel A1 Eleni Mavriopoulou A1 Markus Hohenfellner A1 Frederik Lars Giesel A1 Uwe Haberkorn A1 Clemens Kratochwil YR 2019 UL http://jnm.snmjournals.org/content/60/6/806.abstract AB Because of different physical properties, the β-emitters 177Lu and 90Y offer specific radiologic–biologic advantages in dedicated clinical situations. Our objective was to introduce 90Y-labeled prostate-specific membrane antigen (PSMA)–617 to clinical application, providing additional avenues for personalized medicine. Here, we present our dosimetry estimate for 90Y-PSMA-617, report first clinical experiences, and discuss the advantages and drawbacks of varying the β-emitter in PSMA-targeting radioligand therapy. Methods: To approximate radiation dosimetry, 4 patients with metastatic castration-resistant prostate cancer underwent serially performed imaging up to 1 wk after 177Lu-PSMA-617 therapy. Time–activity curves were extrapolated to the half-life of 90Y, 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 90Y-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. Results: The projected dosimetry for 90Y-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 177Lu-PSMA-617 literature data. Conclusion: A factor 3–4 lower treatment activity for 90Y-PSMA-617 translates into a comparable dosimetry estimate and clinical findings similar to those of 177Lu-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.