BACKGROUND: 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. 
213Bi, that deposit their high energy within a short range allow the selective 
irradiation of tumor cells while sparing adjacent neuronal structures.
MATERIAL AND METHODS: 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 213Bi- DOTA-[Thi8,Met(O2)11]-substance P 
(213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)11]-substance P 
(68Ga-DOTA-SP) was co-injected with the therapeutic doses to assess 
biodistribution using PET/CT. Therapeutic response was monitored with MRI.
RESULTS: Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 
213Bi- 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.
CONCLUSIONS: Targeted alpha therapy of secondary GBM with 213Bi-DOTA-SP is safe 
and well tolerated and may evolve as a promising novel therapeutic option for 
secondary GBM.