The treatment regimen for [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) 617 therapy follows that of chemotherapy: 6 administrations of a fixed activity, each separated by 6 wk. Mathematic modeling can be used to test the hypothesis that the current treatment regimen for a radiopharmaceutical modality is suboptimal. Methods: A mathematic model was developed to describe tumor growth during [¹⁷⁷Lu]Lu-PSMA therapy. The model examined alternative treatment schedules to maximize tumor mass reduction while still maintaining an acceptable biologically effective dose to kidneys. Median patients’ pharmacokinetics from literature reports were used to obtain the dose rate over time. The model incorporates the Gompertz tumor growth and linear quadratic models to describe the effect of radiation-induced cell kill on tumor growth. For a fixed total activity of 44.4 GBq of [¹⁷⁷Lu]Lu-PSMA-617 and a 6-wk interval between cycles, the efficacy of the standard fractionation (6-cycle) treatment schedule was compared with different treatment regimens for a distribution of published tumor masses. A treatment schedule whereby 7.4 GBq are administered in the first cycle, and the remaining activity (37 GBq) in the second cycle (1-2-cycle treatment), was examined. Results: When tumor mass nadir was used as the optimization metric, a lower tumor burden (e.g., <4 g) was insensitive to the number of cycles; the 6-cycle treatment was equivalent to the 1-2-cycle treatment. For larger masses, fewer cycles yielded better results. For a 7-g tumor, the 5-cycle, 4-cycle, 3-cycle and 1-2-cycle schedules were 24%, 50%, 76%, and 84% more efficacious, respectively, than the 6-cycle schedule. The absorbed doses to kidneys, parotid glands, lacrimal glands, and red marrow were 23, 16, 70, and 1 Gy, respectively. In all fractionated schedules, the biologically effective dose to kidneys was within tolerance (<40 Gy). Conclusion: On the basis of model-derived simulations, treatment delivered in a 1-2-cycle schedule is recommended to achieve better outcomes for patients undergoing [¹⁷⁷Lu]Lu-PSMA therapy.

[¹⁷⁷Lu]Lu-前列腺特异性膜抗原 （PSMA） 617 疗法的治疗方案遵循化疗：6 次固定活性给药，每次间隔 6 周。数学模型可用于检验当前放射性药物模式的治疗方案不理想的假设。方法：开发了一个数学模型来描述 [¹⁷⁷Lu]Lu-PSMA 治疗期间的肿瘤生长。该模型检查了替代治疗方案，以最大限度地减少肿瘤质量，同时仍保持可接受的肾脏生物有效剂量。使用文献报告中的中位患者药代动力学来获得随时间变化的剂量率。该模型结合了 Gompertz 肿瘤生长和线性二次模型来描述辐射诱导的细胞杀伤对肿瘤生长的影响。对于 44.4 GBq 的 [¹⁷⁷Lu]Lu-PSMA-617 的固定总活性和周期之间的 6 周间隔，将标准分割 （6 周期） 治疗方案的疗效与不同的治疗方案对已发表的肿瘤块分布进行比较。检查了第一个周期施用 7.4 GBq，第二个周期（1-2 个周期治疗）施用剩余活性 （37 GBq） 的治疗方案。结果：当肿瘤质量最低点用作优化指标时，较低的肿瘤负荷 （例如，<4 g） 对周期数不敏感;6 周期治疗与 1-2 周期治疗相当。对于较大的质量，较少的循环产生更好的结果。对于 7 g 肿瘤，5 周期、4 周期、3 周期和 1-2 周期方案的疗效分别比 6 周期方案高 24% 、 50% 、 76% 和 84%。 对肾脏、腮腺、泪腺和红骨髓的吸收剂量分别为 23 、 16 、 70 和 1 Gy。在所有分割方案中，肾脏的生物有效剂量在耐受范围内 （<40 Gy）。结论：基于模型衍生的模拟，建议以 1-2 个周期的方案进行治疗，以使接受 [¹⁷⁷Lu]Lu-PSMA 治疗的患者获得更好的结果。