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

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 ²¹³Bi allows for selective irradiation and killing of tumor cells. 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 ²¹³Bi-DOTA-Substance P (²¹³Bi-DOTA-SP) in 2-month intervals. ⁶⁸Ga-DOTA-Substance P (⁶⁸Ga-DOTA-SP) was co-injected with ²¹³Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging. Treatment with activity up to 11.2 GBq ²¹³Bi-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 ²¹³Bi-DOTA-SP was 7.5 months. Treatment of recurrent GBM with ²¹³Bi-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 ²²⁵Ac/²¹³Bi radionuclide generators is secured, targeted alpha therapy with ²¹³Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.