Abstract：
Understanding the relationship between lesion-absorbed dose and tumor response in 177Lu-PSMA-617 radiopharmaceutical therapies (RPTs) remains complex. We aimed to investigate whether baseline lesion-absorbed dose can predict lesion-based responses and to explore the connection between lesion-absorbed dose and prostate-specific antigen (PSA) response. Methods: In this retrospective study, we evaluated 50 patients with 335 index lesions undergoing 177Lu-PSMA-617 RPT, who had dosimetry analysis performed on SPECT/CT at 24 h after cycles 1 and 2. First, we identified the index lesions for each patient and measured the lesion-based absorbed doses. Lesion-based response was calculated after cycle 2. Additionally, PSA50 response (a decline of 50% from baseline PSA) after cycle 2 was also calculated. The respective responses for mean and maximum absorbed doses and prostate-specific membrane antigen (PSMA) volumetric intensity product (VIP-PSMA) at cycles 1 and 2 were termed SPECTmean, SPECTmaximum, and SPECTVIP-PSMA, respectively. Results: Of the 50 patients reviewed, 46% achieved a PSA50 response after cycle 2. Of the 335 index lesions, 58% were osseous, 32% were lymph nodes, and 10% were soft-tissue metastatic lesions. The SPECT lesion-based responses were higher in PSA responders than in nonresponders (SPECTmean response of 46.8% ± 26.1% vs. 26.2% ± 24.5%, P = 0.007; SPECTmaximum response of 45% ± 25.1% vs. 19% ± 27.0%, P = 0.001; SPECTVIP-PSMA response of 49.2% ± 30.3% vs. 14% ± 34.7%, P = 0.0005). An association was observed between PSA response and SPECTVIP-PSMA response (R 2 = 0.40 and P < 0.0001). A limited relationship was found between baseline absorbed dose measured with a 24-h single time point and SPECT lesion-based response (R 2 = 0.05, P = 0.001, and R 2 = 0.03, P = 0.007, for mean and maximum absorbed doses, respectively). Conclusion: In this retrospective study, quantitative lesion-based response correlated with patient-level PSA response. We observed a limited relationship between baseline absorbed dose and lesion-based responses. Most of the variance in response remains unexplained solely by baseline absorbed dose. Establishment of a dose-response relationship in RPT with a single time point at 24 h presented some limitations.
摘要：
了解177Lu-PSMA-617放射性药物疗法（RPT）中病变吸收剂量与肿瘤反应之间的关系仍然很复杂。我们旨在研究基线病变吸收剂量是否可以预测基于病变的反应，并探讨病变吸收剂量与前列腺特异性抗原（PSA）反应之间的联系。方法：在这项回顾性研究中，我们评估了50例335个指标病变的患者进行177Lu-PSMA-617RPT，在第1和第2周期后24小时对SPECT/CT进行了剂量学分析。首先,我们确定了每位患者的指标病变,并测量了基于病变的吸收剂量.在第2周期之后计算基于损伤的反应。此外,还计算了第2周期后的PSA50反应(从基线PSA下降50%)。在第1周期和第2周期，对平均和最大吸收剂量和前列腺特异性膜抗原（PSMA）体积强度乘积（VIP-PSMA）的相应反应称为SPECTmean，SPECTmaximum,和SPECTVIP-PSMA,分别。结果：在检查的50例患者中，46%的人在周期2后取得了PSA50反响。在335个指标病变中，58%是骨性的，32%是淋巴结，10%为软组织转移灶。PSA反应者的SPECT病变反应高于无反应者（SPECTmean反应为46.8％±26.1％与26.2%±24.5%,P=0.007;SPECTT最大响应为45%±25.1%vs.19%±27.0%，P=0.001;SPECTVIP-PSMA反应49.2%±30.3%vs.14%±34.7%，P=0.0005)。PSA反应与SPECTVIP-PSMA反应之间存在相关性（R2=0.40，P<0.0001）。在24小时单次时间点测量的基线吸收剂量与基于SPECT病变的反应之间存在有限的关系（对于平均和最大吸收剂量，R2=0.05，P=0.001，R2=0.03，P=0.007，分别)。结论：在这项回顾性研究中，基于病变的定量反应与患者水平PSA反应相关。我们观察到基线吸收剂量和基于病变的反应之间的有限关系。反应中的大多数差异仍然不能仅由基线吸收剂量来解释。在24小时的单个时间点建立RPT的剂量-反应关系存在一些局限性。
