Department of Nuclear Medicine, Medical University of Warsaw, ul. Banacha 1 a, 02-097, Warsaw, Poland.
European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany.
Eur J Nucl Med Mol Imaging. 2018 Jul;45(9):1636-1644. doi: 10.1007/s00259-018-4015-2. Epub 2018 Apr 30.
Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures.
Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1-6 doses of 0.9-2.3 GBq Bi- DOTA-[Thi,Met(O)]-substance P (Bi-DOTA-SP) in 2-month intervals. Ga-DOTA-[Thi,Met(O)]-substance P (Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI.
Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.
Targeted alpha therapy of secondary GBM with Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.
多形性胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤，主要表现为原发性初发性和较少表现为继发性神经胶质瘤。GBM 已被证明过度表达 NK-1 受体，而物质 P 可用作靶向治疗的配体。α发射体，例如 Bi，其在短距离内沉积其高能量允许选择性地辐照肿瘤细胞，同时使相邻的神经元结构免受伤害。
在华沙医科大学迄今已接受靶向 α 治疗的 50 名不同亚型的胶质瘤患者中，我们在此报告了 9 名继发性 GBM 患者的数据。在手术后、化疗和放疗后，复发的 GBM 通过腔内注射 0.9-2.3GBq Bi-DOTA-[Thi，Met（O）]-物质 P（Bi-DOTA-SP）1-6 次进行治疗，间隔 2 个月。将 Ga-DOTA-[Thi，Met（O）]-物质 P（Ga-DOTA-SP）与治疗剂量共同注射，使用 PET/CT 评估生物分布。使用 MRI 监测治疗反应。
使用从 1.4 到 9.7（中位数 5.8）GBq 的 Bi-DOTA-SP 的治疗活动耐受性良好，只有轻微的短暂不良反应，主要是由于短暂的局灶性水肿反应引起的头痛。开始 α 治疗后，无进展生存和总生存时间的中位数分别为 5.8 和 16.4 个月。首次诊断后的中位总生存时间为 52.3 个月。在开始治疗后 39 和 51 个月，9 名患者中有 2 名仍然存活。
用 Bi-DOTA-SP 进行继发性 GBM 的靶向 α 治疗是安全且耐受良好的，可能成为继发性 GBM 的一种有前途的新型治疗选择。
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