Targeted alpha-radionuclide therapy of functionally critically located gliomas with ²¹³Bi-DOTA-[Thi⁸,Met(O₂)¹¹]-substance P: a pilot trial

Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting Y-90-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of Y-90 may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide Bi-213 with a mean tissue range of 81 A mu m may have a more favourable toxicity profile. Therefore, we evaluated locally injected Bi-213-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, Bi-213-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. Targeted radiopeptide therapy using Bi-213-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. Bi-213-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. This study provides proof of concept that targeted local radiotherapy using Bi-213-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis.