225Ac-PSMA-617 for therapy of prostate cancer
Prostate-specific membrane antigen (PSMA)-targeting radio-ligand therapy with beta-emitting 177Lutetium has already been investigated in several early phase dosimetry studies, demonstrated promising results in phase-2, and recently the first phase-3 trial finished recruitment. In contrast, PSMA-targ...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
14 February 2020
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| In: |
Seminars in nuclear medicine
Year: 2020, Volume: 50, Issue: 2, Pages: 133-140 |
| ISSN: | 1558-4623 |
| DOI: | 10.1053/j.semnuclmed.2020.02.004 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1053/j.semnuclmed.2020.02.004 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0001299820300052 
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| Author Notes: | Clemens Kratochwil, Uwe Haberkorn, and Frederik Lars Giesel |
| Summary: | Prostate-specific membrane antigen (PSMA)-targeting radio-ligand therapy with beta-emitting 177Lutetium has already been investigated in several early phase dosimetry studies, demonstrated promising results in phase-2, and recently the first phase-3 trial finished recruitment. In contrast, PSMA-targeting alpha-particle therapy (TAT) has only been evaluated in few preclinical experiments, preliminary dosimetry attempts and some retrospective observational studies, yet. First clinical experience with 225Ac-PSMA-617 demonstrates promising antitumor activity with a 63%-70% PSA>50%-response rate, 10-15 months duration of response and complete remissions in approximately ten percent of patients, some of them with enduring relapse-free survival. Nevertheless, without comparative trials there is no prove whether, applied in identical clinical situations, 225Ac-PSMA-617 is really more efficiently than 177Lu-PSMA-617 or vice versa. However, there is some good rationale, that PSMA-TAT might have advantages in particular clinical indications. This includes patients with diffuse type red-marrow infiltration by reducing off-target radiation to surrounding cells; ablation of micrometastases after favorable response to other previous therapy or someday in early stage disease. Also treatment escalation of patients, either with poor response to 177Lu-PSMA or harboring adverse prognostic biomarkers, appears promising. In preclinical research, alpha-radiation demonstrated stronger induction of abscopal effects than beta-radiation; favoring its usage as a combination partner with immunotherapies. So, further evaluation of PSMA-TAT is definitely warranted. Recently, de-escalated treatment protocols and application of 225Ac/177Lu-PSMA “cocktail”-regimens improved the tolerability of 225Ac-PSMA-617 TAT, reducing the risk for development dry-mouth syndrome. This opens new avenues for future application in earlier stage disease. |
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| Item Description: | Die Zahl "225" im Titel ist hochgestellt Gesehen am 23.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1558-4623 |
| DOI: | 10.1053/j.semnuclmed.2020.02.004 |