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

Purpose: 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 90Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5mm of 90Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide 213Bi with a mean tissue range of 81µm may have a more favourable toxicity profile. Therefore, we evaluated locally injected 213Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. Methods: In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, 213Bi-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. Results: Targeted radiopeptide therapy using 213Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. 213Bi-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. Conclusion: This study provides proof of concept that targeted local radiotherapy using 213Bi-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 prognosi

Effects of thermal shocks on the release of radioisotopes and on molten metal target vessels

The ISOLDE pulsed proton beam peak power amounts to 500 MW during the 2.4 ms proton pulse. The fraction of the proton pulse energy deposited in the target material is at the origin of severe thermal shocks. Quantitative measurement of their effect on the release of radioelements from ISOLDE targets was obtained by comparison of release profiles measured under different proton beam settings. The thermal shock induced in liquids (Pb, Sn, La) lead to mechanical failure of ISOLDE molten metal target vessels. Failure analysis is presented and discussed in the light of the response of mercury samples submitted to the ISOLDE beam and monitored by high-speed optical systems