First clinical experience with 90Y-PSMA-617 - Is there a rationale for varying the radionuclide in PSMA-RLT?
2018
527 Purpose: Prostate cancer often presents a heterogeneous PSMA expression pattern. If PSMA-RLT would be based on high energy beta particle emitters with several millimeter tissue penetration range, a more homogenous radiation dose distribution could be achieved by increasing the cross-fire effect to cell clones with less inherent PSMA expression. Our objective was to introduce 90Y-PSMA-617 to clinical application, providing additional avenues for personalized tailored RLT. Methods: Four patients with mCRPC had already undergone serially performed imaging scans up to 8 days p.i. as part of a 177Lu-dosimetry. Their time-activity-curves were extrapolated to the half-life of 90Y and the OLINDA-dosimetry was repeated using the newly integrated cumulated activities. Based on this dosimetry estimate, we defined a treatment protocol which should be widely dose equivalent to our 177Lu-PSMA-617 standard protocol. In clinical practice 10 patients with PSMA-positive lymphonodal bulk disease were stratified to received 90Y-PSMA-617 RLT (mean 3.2 GBq; range 2.8-3.7 GBq); after therapy safety lab tests, 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 a salivary glands dose of 5.57 ± 1.34 Gy/GBq; Metastases were approximated with 22.8 ± 16.10 Gy/GBq. In the treatment case series, the observed acute hematological toxicity (grade-1 leucopenia n=1, grade-1 thrombocytopenia n=2) and clinical side-effects (transient xerostomia n=1, nausea n=1) as well as PSA-response (6/10 patients any PSA response, 3/10 patients >50% PSA decline) was comparable to 177Lu-PSMA-617 literature data. Conclusions: Activities of 2.8GBq 90Y-PSMA-617 are widely dose-equivalent to a 3.5-fold higher activity of 177Lu-PSMA-617. 90Y-PSMA-617 provides theoretical advantages in the setting of bulk disease, while 177Lu-PSMA-617 should be preferred for small lesions or multiple bone metastases. It remains an open question, if personalized treatment concepts really improve clinical outcome.
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