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Lu-PSMA-617 剂量测定:甘露糖醇输注和谷氨酸片剂给药后的剂量测定:EUDRACT/RSO 2016-002732-32IRST 方案的初步结果。

Dosimetry of Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol.

机构信息

Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

Oncology Pharmacy, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.

出版信息

Molecules. 2019 Feb 11;24(3):621. doi: 10.3390/molecules24030621.

Abstract

Radio-ligand therapy (RLT) withLu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53⁻85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16⁻24 h, 36⁻48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6⁻60.7) for PGs, 31.4 h (12.2⁻80.6) for kidneys, 8.2 h (2.5⁻14.7) for RM and 40.1 h (31.6⁻79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33⁻2.63) for PGs, 0.70 mGy/MBq (0.26⁻1.07) for kidneys, 0.044 mGy/MBq (0.023⁻0.067) for RM and 0.04 mGy/MBq (0.02⁻0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

摘要

放射性配体治疗 (RLT) 联合 Lu-PSMA-617 是转移性去势抵抗性前列腺癌 (mCRPC) 患者的一种很有前景的选择。一项正在意大利马尔多拉的IRST 进行的 mCRPC 前瞻性 II 期研究 (EUDRACT/RSO,2016-002732-32) 正在招募 9 名患者(中位年龄:68 岁,范围:53⁻85)进行腮腺 (PG)、肾脏、红骨髓 (RM) 和全身 (WB) 的剂量评估。口服叶酸多聚谷氨酸片作为 PG 保护剂,静脉输注 500 mL 10%甘露醇溶液以减少肾脏摄取。在输注后不同时间(1 h、16⁻24 h、36⁻48 h 和 120 h)采集全身平面图像 (WBI) 和血样。使用 MIRD 形式主义 (OLINDA/EXM 软件) 进行剂量计算。PG 的中位有效半衰期为 33.0 h(范围:25.6⁻60.7),肾脏为 31.4 h(12.2⁻80.6),RM 为 8.2 h(2.5⁻14.7),WB 为 40.1 h(31.6⁻79.7)。PG 的中位剂量为 0.48 mGy/MBq(范围:0.33⁻2.63),肾脏为 0.70 mGy/MBq(0.26⁻1.07),RM 为 0.044 mGy/MBq(0.023⁻0.067),WB 为 0.04 mGy/MBq(0.02⁻0.11)。与之前发表的剂量学数据进行了比较,发现 PG 有显著差异,而肾脏无显著差异。对于 PG,在 RLT 期间给予谷氨酸片以减少摄取的可能性似乎是可行的,而进一步的研究对于更集中地评估肾脏摄取的减少是必要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d82/6385027/df6261b5ccd0/molecules-24-00621-g001.jpg

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