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

Ziel/Aim 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, ²¹³Bi was used for labeling of SP; Bi is convenient for labeling of peptides, and short half-life of ²¹³Bi is beneficial for radiation protection. Currently, ²²⁵Ac was introduced. It seems that a diverse range of energy, as well as longer T_1/2 should favour a better distribution of the radiopharmaceutical into the tumor.

Methodik/Methods 13 patients with histologically confirmed recurrence of the glia tumor grade II-IV were treated: group A - patients with grade II - III WHO (n = 5), group B - patients with grade IV (n = 8). 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.

Ergebnisse/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.

Schlussfolgerungen/Conclusions 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.