PSMA 靶向放射性配体疗法对恶性原发性和继发性脑肿瘤的潜在作用：采用超选择性动脉内给药的单中心、开放标签、非随机前瞻性影像学研究。

Potential of PSMA-targeting radioligand therapy for malignant primary and secondary brain tumours using super-selective intra-arterial administration: a single centre, open label, non-randomised prospective imaging study.

机构信息

Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Brain Tumour Centre, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.

Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.

出版信息

EBioMedicine. 2024 Apr;102:105068. doi: 10.1016/j.ebiom.2024.105068. Epub 2024 Mar 22.

DOI:10.1016/j.ebiom.2024.105068

PMID:38518652

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10981001/

Abstract

BACKGROUND

The aim of this study was to provide quantitative evidence for the potential of PSMA-targeting radioligand therapy (RLT) as treatment approach for malignant brain tumours, and to explore whether tumour uptake could be enhanced by super-selective intra-arterial (ssIA)-administration.

METHODS

Ten patients (n = 5 high-grade glioma, n = 5 brain metastasis) received 1.5 MBq/kg [Ga]Ga-PSMA-11 intravenously and, within 7 days, intra-arterially (i.e., selectively in tumour-feeding arteries), followed twice by PET-MRI at 90, 165 and 240 min post-injection. Patient safety was monitored for each procedure. Standardised uptake values (SUVs) were obtained for tumour, healthy-brain, salivary glands and liver. Tumour-to-salivary-gland (T/SG) and tumour-to-liver (T/L) uptake-ratios were calculated.

FINDINGS

No adverse events requiring study termination occurred. All patients showed uptake of [Ga]Ga-PSMA-11 at the tumour site. Uptake was a median 15-fold higher following ssIA-administration (SUVmax median: 142.8, IQR: 102.8-245.9) compared to IV-administration (10.5, IQR:7.5-13.0). According to the bootstrap analysis, mean SUVmax after ssIA (168.8, 95% CI: 110.6-227.0) was well beyond the 95% confidence-interval of IV administration (10.5, 95% CI: 8.4-12.7). Uptake in healthy-brain was negligible, independent of administration route (SUVmean <0.1-0.1). Off-target uptake was comparable, resulting in more favourable T/SG- and T/L-ratios of 8.4 (IQR: 4.4-11.5) and 26.5 (IQR: 14.0-46.4) following ssIA, versus 0.5 (IQR: 0.4-0.7) and 1.8 (IQR: 1.0-2.7) for IV-administration.

INTERPRETATION

ssIA-administration is safe and leads to a median fifteen-fold higher radioligand uptake at the tumour site, therewith qualifying more patients for treatment and enhancing the potential of therapy. These results open new avenues for the development of effective RLT-based treatment strategies for patients with brain tumours.

FUNDING

Semmy Foundation.

摘要

背景

本研究旨在为 PSMA 靶向放射性配体治疗（RLT）作为恶性脑肿瘤治疗方法的潜力提供定量证据，并探讨肿瘤摄取是否可以通过超选择性动脉内（ssIA）给药来增强。

方法

10 名患者（n=5 例高级别胶质瘤，n=5 例脑转移瘤）静脉内给予 1.5 MBq/kg [Ga]Ga-PSMA-11，7 天内选择性动脉内（即肿瘤供血动脉内）给药，然后在注射后 90、165 和 240 分钟进行两次 PET-MRI。监测每位患者的每个程序的安全性。获得肿瘤、健康脑、唾液腺和肝脏的标准化摄取值（SUVs）。计算肿瘤与唾液腺（T/SG）和肿瘤与肝脏（T/L）摄取比。

结果

没有发生需要终止研究的不良事件。所有患者在肿瘤部位均显示出 [Ga]Ga-PSMA-11 的摄取。与静脉内给药（SUVmax 中位数：10.5，IQR：7.5-13.0）相比，ssIA 给药后摄取中位数增加了 15 倍（SUVmax 中位数：142.8，IQR：102.8-245.9）。根据自举分析，ssIA 后平均 SUVmax（168.8，95%CI：110.6-227.0）远远超过 IV 给药的 95%置信区间（10.5，95%CI：8.4-12.7）。无论给药途径如何，健康脑的摄取都可以忽略不计（SUVmean <0.1-0.1）。非靶组织摄取相似，导致 ssIA 后更有利的 T/SG 和 T/L 比值为 8.4（IQR：4.4-11.5）和 26.5（IQR：14.0-46.4），而 IV 给药为 0.5（IQR：0.4-0.7）和 1.8（IQR：1.0-2.7）。