Zaid Nouran R R, Bastiaannet Remco, Hobbs Rob, Sgouros George
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; and
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
J Nucl Med. 2025 Jan 3;66(1):84-90. doi: 10.2967/jnumed.124.268457.
The treatment regimen for [Lu]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. A mathematic model was developed to describe tumor growth during [Lu]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 [Lu]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. 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). On the basis of model-derived simulations, treatment delivered in a 1-2-cycle schedule is recommended to achieve better outcomes for patients undergoing [Lu]Lu-PSMA therapy.
[镥]镥-前列腺特异性膜抗原（PSMA）617治疗的方案遵循化疗方案：固定活度给药6次，每次间隔6周。数学建模可用于检验放射性药物治疗当前方案并非最优的假设。开发了一个数学模型来描述[镥]镥-PSMA治疗期间的肿瘤生长情况。该模型研究了替代治疗方案，以在使肿瘤质量减少最大化的同时，仍保持对肾脏可接受的生物有效剂量。利用文献报道的患者药代动力学中位数来获取随时间变化的剂量率。该模型结合了Gompertz肿瘤生长模型和线性二次模型，以描述辐射诱导的细胞杀伤对肿瘤生长的影响。对于[镥]镥-PSMA-617固定总活度为44.4 GBq且周期之间间隔6周的情况，针对已发表的肿瘤质量分布，将标准分次（6周期）治疗方案的疗效与不同治疗方案进行了比较。研究了一种治疗方案，即第一周期给予7.4 GBq，第二周期给予剩余活度（37 GBq）（1 - 2周期治疗）。当将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。对于较大的肿瘤质量，较少的周期产生更好的结果。对于7 g的肿瘤，5周期、4周期、3周期和1 - 2周期方案分别比6周期方案有效24%、50%、76%和84%。肾脏（23 Gy）、腮腺（16 Gy）、泪腺（70 Gy）和红骨髓（1 Gy）的吸收剂量。在所有分次方案中，对肾脏的生物有效剂量均在耐受范围内（<40 Gy）。基于模型模拟结果，建议采用1 - 2周期方案进行治疗，以使接受[镥]镥-PSMA治疗的患者获得更好的疗效。
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