First-Strike Rapid Predictive Dosimetry and Dose Response for 177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer.

IF 1 Q4 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Yung Hsiang Kao, Nadia Falzone, Michael Pearson, Dinesh Sivaratnam
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引用次数: 0

Abstract

We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177Lu-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/cm3) 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.

转移性钙化抗性前列腺癌 177Lu-PSMA 治疗的首次快速预测剂量测定和剂量反应。
我们设计了一种针对转移性耐受性前列腺癌的 177Lu-PSMA-I&T 快速个性化预测剂量测量方案,并进行了临床验证。它取代了传统的经验处方,为首次打击优化提供了具有临床意义的预测吸收剂量。方法:前列腺特异性膜抗原 PET前列腺特异性膜抗原 PET 被视为一种模拟研究,可捕捉肿瘤、骨髓和肾脏在单个时间点的复杂剂量相互作用。研究中引入了分层、异质性、正常器官限制(骨髓、肾脏)、吸收剂量和剂量率等辐射原理。我们以免费、开源、用户友好的电子表格形式创建了一个预测计算器,可在几分钟内完成。我们的方案通过对组织辐射浓度(kBq/cm3)进行取样,结合用户反映剂量学先决条件的临床输入进行分析,从而实现了速度和准确性。骨髓吸收剂量限制为每分 0.217 Gy(剂量率≤0.0147 Gy/h),分次间间隔至少 6 周。结果对首批 10 名患者进行了分析。任何前列腺特异性抗原(PSA)反应的首次平均肿瘤吸收剂量阈值均超过 10 Gy(剂量率,>0.1 Gy/h)。肿瘤首次吸收剂量最低的转移灶与前列腺特异性抗原(PSA)下降百分比的相关性最好;其达到假定的零PSA阈值为20 Gy或更高。每位患者的 PSA 倍增时间可用于个性化定制其独特的吸收剂量-反应阈值。在骨髓吸收剂量率的限制下,预测的平均首次启动处方为 11.0 ± 4.0 GBq。高有利条件(肿瘤汇效应)在剂量学上表现为骨髓中肿瘤与正常器官的比率超过 150,肾脏中肿瘤与正常器官的比率超过 4。我们的方案排除了 SUV 作为预测参数的传统作用。结论:我们的快速方案可以在任何繁忙的实际治疗单位中实施,并超过了当今的最佳实践标准。我们的剂量学阈值和预测参数可以从放射生物学角度合理地确定每位患者的首次照射剂量,精确到一个贝克勒尔。肿瘤与正常器官之间的有利比率可通过预测剂量学进行前瞻性利用,以优化首次照射剂量。我们方案的科学框架可应用于其他系统性放射性核素疗法。
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来源期刊
Journal of nuclear medicine technology
Journal of nuclear medicine technology RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
CiteScore
1.90
自引率
15.40%
发文量
57
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