Lesion Absorbed Dose–Response Relationship in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy

Milan Grkovski, Simone S. Krebs, Joseph A. O’Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J. Fox, Neeta Pandit-Taskar, Mark P. Dunphy, Lisa Bodei, John L. Humm, Heiko Schöder
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Abstract

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD–response relationship at both the patient and lesion levels. Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the SUVmax before, during, and after RPT with [68Ga]Ga-PSMA-11 PET/CT. Results: Baseline PET and SPECT lesion SUVmax were strongly correlated (Pearson r, 0.74; n = 1364 lesions). Kidney ADs were relatively low (0.28 ± 0.12 Gy/GBq). No significant decrease in estimated glomerular filtration rate was observed 1 y after RPT. On average, STP dosimetry underestimated the AD by 8%. A moderate negative relationship was observed between the mean lesion AD for an individual patient (Spearman ρ, −0.33; n = 63) and lesion (Spearman ρ, −0.30; n = 681) responses. Patients receiving a higher mean AD (>7.5 Gy) had a significantly better prostate-specific antigen response (median, 70% vs. −5%; P < 0.001; unpaired t test) and longer biochemical progression-free survival (median, 4.1 mo vs. 1.6 mo; P = 0.005; unpaired t test) compared with patients whose mean AD was less than 7.5 Gy, respectively. Conclusion: A moderate AD–response relationship was observed in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT. The feasibility of STP dosimetry facilitates its implementation for treatment personalization. Kidney ADs may be reduced with abundant hydration.

转移性去势抵抗性前列腺癌患者接受放射药物治疗的病灶吸收剂量-反应关系[177Lu]
转移性去势抵抗性前列腺癌患者接受[177Lu]Lu-PSMA-617放射药物治疗(RPT)时,病变吸收剂量(AD)与反应之间的关系尚不清楚。这项工作的目的是研究ad反应在患者和病变水平的关系。方法:65例患者接受7.31±0.27 GBq的[177Lu]Lu-PSMA-617治疗后行SPECT/CT连续显像。进行单时间点(STP) (Hänscheid 72 h近似值)和多时间点体向剂量测定。通过RPT第1周期前后血清前列腺特异性抗原水平的变化来评估患者的反应。通过使用[68Ga]Ga-PSMA-11 PET/CT检测RPT前、中、后的SUVmax变化来评估单个病变的反应。结果:基线PET与SPECT病变SUVmax呈强相关(Pearson r, 0.74;N = 1364个病灶)。肾脏ADs较低(0.28±0.12 Gy/GBq)。RPT后1 y未观察到肾小球滤过率的显著降低。平均而言,STP剂量法低估了8%的AD。单个患者的平均病变AD呈中等负相关(Spearman ρ, - 0.33;n = 63)和病变(Spearman ρ,−0.30;N = 681)。接受较高平均AD (>7.5 Gy)的患者具有更好的前列腺特异性抗原应答(中位数,70% vs - 5%;P & lt;0.001;Unpaired t检验)和更长的生化无进展生存期(中位,4.1个月vs. 1.6个月;P = 0.005;非配对t检验),与平均AD小于7.5 Gy的患者相比。结论:转移性去势抵抗性前列腺癌患者接受[177Lu]Lu-PSMA-617 RPT治疗时ad反应存在中等程度的相关性。STP剂量法的可行性有利于治疗个性化的实施。充足的水合作用可降低肾脏ad。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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