Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
J Nucl Med. 2019 Apr;60(4):517-523. doi: 10.2967/jnumed.118.219352. Epub 2018 Oct 5.
Lu-prostate-specific membrane antigen (PSMA)-617 enables targeted delivery of β-particle radiation to prostate cancer. We determined its radiation dosimetry and relationships to pretherapeutic imaging and outcomes. Thirty patients with prostate cancer receiving Lu-PSMA-617 within a prospective clinical trial (ACTRN12615000912583) were studied. Screening Ga-PSMA-11 PET/CT demonstrated high PSMA expression in all patients. After therapy, patients underwent quantitative SPECT/CT at 4, 24, and 96 h. Pharmacokinetic uptake and clearance at a voxel level were calculated and translated into absorbed dose using voxel S values. Volumes of interest were drawn on normal tissues and tumor to assess radiation dose, and a whole-body tumor dose was defined. Correlations between PSMA PET/CT parameters, dosimetry, and biochemical and therapeutic response were analyzed to identify relationships between absorbed dose, tumor burden, and patient physiology. Mean absorbed dose to kidneys, submandibular and parotid glands, liver, spleen, and bone marrow was 0.39, 0.44, 0.58, 0.1, 0.06, and 0.11 Gy/MBq, respectively. Median whole-body tumor-absorbed dose was 11.55 Gy and correlated with prostate-specific antigen (PSA) response at 12 wk. A median dose of 14.1 Gy was observed in patients achieving a PSA decline of at least 50%, versus 9.6 Gy for those achieving a PSA decline of less than 50% ( < 0.01). Of 11 patients receiving a tumor dose of less than 10 Gy, only one achieved a PSA response of at least 50%. On screening PSMA PET, whole-body tumor SUV correlated with mean absorbed dose ( = 0.62), and SUV of the parotids correlated with absorbed dose ( = 0.67). There was an inverse correlation between tumor volume and mean dose to the parotids ( = -0.41) and kidneys ( = -0.43). The mean parotid dose was also reduced with increasing body mass ( = -0.41) and body surface area ( = -0.37). Lu-PSMA-617 delivers high absorbed doses to tumor, with a significant correlation between whole-body tumor dose and PSA response. Patients receiving less than 10 Gy were unlikely to achieve a fall in PSA of at least 50%. Significant correlations between aspects of screening Ga-PET/CT and tumor and normal tissue dose were observed, providing a rationale for patient-specific dosing. Reduced salivary and kidney doses were observed in patients with a higher tumor burden. The parotid dose also reduced with increasing body mass and body surface area.
Lu-前列腺特异性膜抗原（PSMA）-617 能够将β粒子辐射靶向递送至前列腺癌。我们确定了其辐射剂量学，并与治疗前的影像学和结果建立了关系。 在一项前瞻性临床试验（ACTRN12615000912583）中，对 30 名接受 Lu-PSMA-617 治疗的前列腺癌患者进行了研究。筛选 Ga-PSMA-11 PET/CT 显示所有患者的 PSMA 表达均较高。治疗后，患者在 4、24 和 96 小时接受定量 SPECT/CT 检查。以体素水平计算摄取和清除的药代动力学，并使用体素 S 值将其转化为吸收剂量。在正常组织和肿瘤上绘制感兴趣的体积以评估辐射剂量，并定义全身肿瘤剂量。分析 PSMA PET/CT 参数、剂量学以及生化和治疗反应之间的相关性，以确定吸收剂量、肿瘤负荷和患者生理之间的关系。 肾脏、颌下腺和腮腺、肝脏、脾脏和骨髓的平均吸收剂量分别为 0.39、0.44、0.58、0.1、0.06 和 0.11 Gy/MBq。中位全身肿瘤吸收剂量为 11.55 Gy，与 12 周时的 PSA 反应相关。在 PSA 下降至少 50%的患者中观察到 14.1 Gy 的中位肿瘤剂量，而 PSA 下降小于 50%的患者为 9.6 Gy（<0.01）。在接受肿瘤剂量小于 10 Gy 的 11 名患者中，只有 1 名患者的 PSA 反应至少下降 50%。在筛选 PSMA PET 上，全身肿瘤 SUV 与平均吸收剂量相关（ = 0.62），而腮腺的 SUV 与吸收剂量相关（ = 0.67）。肿瘤体积与腮腺（ = -0.41）和肾脏（ = -0.43）的平均剂量呈负相关。腮腺剂量也随体质量（ = -0.41）和体表面积（ = -0.37）的增加而降低。Lu-PSMA-617 可向肿瘤输送高吸收剂量，全身肿瘤剂量与 PSA 反应之间存在显著相关性。接受剂量低于 10 Gy 的患者不太可能 PSA 下降至少 50%。观察到 Ga-PET/CT 和肿瘤及正常组织剂量的各个方面之间存在显著相关性，为患者特异性给药提供了依据。在肿瘤负担较高的患者中，唾液腺和肾脏的剂量降低。随着体质量和体表面积的增加，腮腺剂量也降低。
