Safety and efficacy of targeted alpha therapy with 213 Bi-DOTA-substance P in recurrent glioblastoma

Abstract

Abstract: Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter 213 Bi allows for selective irradiation and killing of tumor cells. Material and methods: Twenty patients with recurrent GBM were included into the study following a standard therapy. 1–2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1–7 doses of 213 Bi-DOTA-Substance P ( 213 Bi-DOTA-SP) in 2-month intervals. 68 Ga-DOTA-Substance P ( 68 Ga-DOTA-SP) was co-injected with 213 Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging. Results: Treatment with activity up to 11.2 GBq 213 Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of 213 Bi-DOTA-SP was 7.5 months. Conclusions: Treatment of recurrent GBM with 213 Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity 225 Ac/ 213 Bi radionuclide generators is secured, targeted alpha therapy with 213 Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.