Targeted alpha therapy of recurrent glia tumors : clinical experience with 225Ac-Substance-P

Aim/Introduction: Treatment of patients with recurrent glioma is very limited. Introduction of new options of treatment is critically important for this group of patients. Gliomas are characterized by a high expression of receptors for Substance -P (SP), regardless of the histological grading. Therefore, SP labeled with alpha emitters was used for local application into the tumour. Local application reduces systemic adverse effects of the drug as well as the protective effect of the Blood-Brain- Barrier. Moreover, alpha rays have many advantages: tissue range is less than 100 μm; hypoxia and cell cycle are not critical to the effect of radiation. Initially, 213 Bi was used for labeling of SP; bismuthium is convenient for labeling of peptides, and short T1/2 of 213Bi (T1/2 = 46 min) is beneficial for radiation protection. Currently, 225Ac was introduced. It seems that a diverse range of energy, as well as longer T1/2 (10 days) should favor a better distribution of the radiopharmaceutical into the tumor. Materials and Methods: 13 patients with histologically confirmed recurrence of the glia tumor grade II-IV were treated: group A - patients with grade II - III WHO (5 patients), group B - patients with grade IV (8 patients). All patients received a standard treatment (surgery + radio-chemo-therapy). When a recurrence/progression was diagnosed, an intracavitary/ intratumoral injection of 20-40 MBq 225Ac-SP was applied every 2 months (1-7 injections). Monitoring of toxicity and overall survival was indicated as the first goal of the study. The study was approved by the Ethical Committee of the Medical University of Warsaw. Results: In group A: PFS was 4.8 (median) months, OS from primary diagnosis was 114.7 months, OS from diagnosis of recurrence - 38.0 months, and OS from start of radioisotopic treatment - 26.5 months. In group B: : PFS was 3.0 (median) months, OS from primary diagnosis was 21.3 months, OS from diagnosis of recurrence - 10.9 months, and OS from start of radioisotopic treatment - 5.0months. Conclusion: Intracavitary/ intratumoral injection of 225Ac-substance P is tolerated well. Only mild temporary adverse effects (edema, epileptic seizures, aphasia) were observed. It seems that the presented method using 225Ac is promising and requires further clinical trials.

KROLICKI Leszek;  BRUCHERTSEIFER Frank;  KUNIKOWSKA Jolanta;  KOZIARA H;  KROLICKI B;  JAKUCINSKI M;  PAWLAK Dariusz;  APOSTOLIDIS Christos;  ROLA R;  MERLO A.;  MORGENSTERN Alfred; 

2020-01-17

SPRINGER

JRC118234

1619-7070 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC118234,   

10.1007/s00259-019-04486-2 (online),