目的:177Lutetium[Lu]Ludotadipp是一种新型的前列腺特异性膜抗原靶向治疗剂,其添加了白蛋白基序以增加肿瘤的摄取。我们评估了[177Lu]Ludotadipp在转移性去势抵抗性前列腺癌(mCRPC)患者中的生物分布和剂量学。
方法:来自25名患者的数据(中位年龄,73年;范围,60-90)与mCRPC进行了I期研究,并进行了单次给药[177Lu]Ludotadipp(1.85、2.78、3.70、4.63和5.55GBq)的活性升级设计。唾液腺中的活动,肺,肝脏,肾脏,根据[177Lu]Ludotadipp给药后2、24、48、72和168小时采集的全身扫描和腹部SPECT/CT图像估计脾脏。从在3、10、30、60和180分钟获得的血液样本计算红骨髓活性,以及给药后24、48和72小时。使用IDAC-剂量2.1进行基于器官和肿瘤的吸收剂量计算。
结果:正常器官的吸收剂量系数(平均值±标准差)为1.17±0.81Gy/GBq,肺0.05±0.02Gy/GBq,肝脏为0.14±0.06Gy/GBq,肾脏为0.77±0.28Gy/GBq,脾脏为0.12±0.06Gy/GBq,红骨髓为0.07±0.02Gy/GBq。肿瘤的吸收剂量系数为10.43±7.77Gy/GBq。
结论:[177Lu]预计Ludotadipp在计划进行II期临床试验的3.7GBq乘以6个周期的剂量下是安全的,肾脏和骨髓是关键器官,并显示出高肿瘤吸收剂量。
OBJECTIVE: 177Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [177Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC).
METHODS: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I
study with activity escalation design of single administration of [177Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [177Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organ- and tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1.
RESULTS: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq.
CONCLUSIONS: [177Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical
trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.