First-Strike Rapid Predictive Dosimetry and Dose Response for 177 Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer.
| Autor: | Kao YH; Department of Nuclear Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia; yung.kao@mh.org.au., Falzone N; GenesisCare Theranostics, North Shore Health Hub, Sydney, New South Wales, Australia., Pearson M; Medical Imaging Department, Cabrini Hospital, Malvern, Victoria, Australia; and., Sivaratnam D; Department of Nuclear Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.; Medical Imaging Department, Cabrini Hospital, Malvern, Victoria, Australia; and.; GenesisCare Theranostics, Cabrini Hospital, Malvern, Victoria, Australia. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of nuclear medicine technology [J Nucl Med Technol] 2024 Sep 05; Vol. 52 (3), pp. 212-218. Date of Electronic Publication: 2024 Sep 05. |
| DOI: | 10.2967/jnmt.123.267067 |
| Abstrakt: | We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177 Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Methods: Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point. Radiation principles of fractionation, heterogeneity, normal-organ constraints (marrow, kidney), absorbed dose, and dose rate were introduced. We created a predictive calculator in the form of a free, open-source, and user-friendly spreadsheet that can be completed within minutes. Our schema achieves speed and accuracy by sampling tissue radioconcentrations (kBq/cm 3 ) to be analyzed in conjunction with clinical input from the user that reflect dosimetric preconditions. The marrow-absorbed dose constraint was 0.217 Gy (dose rate, ≤0.0147 Gy/h) per fraction with an interfraction interval of at least 6 wk. Results: Our first 10 patients were analyzed. The first-strike mean tumor-absorbed dose threshold for any prostate-specific antigen (PSA) response was more than 10 Gy (dose rate, >0.1 Gy/h). The metastasis with the lowest first-strike tumor-absorbed dose correlated the best with the percentage decrease of PSA; its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose-response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor-to-normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Conclusion: Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor-to-normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.) |
| Databáze: | MEDLINE |
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