Therapy of Patients with Malignant Glioma with Targeted A-Radionuclide Therapy Using 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P

The prognosis of patients with malignant glioma is very poor. New therapy options are mandatory. Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently over-expressed in malignant gliomas and surrounding tumor vessels. Administration of 90Y-DOTA-[Thi8, Met (O o)11]-Substanz P was shown to be feasible and safe. However, in critically located tumors, the mean tissue range of 5 mm of 90Y may lead to unacceptable damage of adjacent, functional critical areas of the brain. We report a phase I study with locally administered 213Bi labeled DOTA-[Thi8, Met (O o)11]-Substanz P in patients with malignant glioma. By using a direct, intratumoral injection, the problem of the short physical half life of Bismuth-213 can be circumvent. To date, 5 patients with malignant glioma (2 Grade IV, 1 Grade III and 2 grade II) without previous treatment were included. One to three catheter systems were placed stereotactically into the tumor. After a diagnostic injection with 111In-DOTA-[Thi8, Met (Oo)11]-Substanz P and subsequent dosimetry, totally 30 to 138 mCi of 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P was injected intratumorally performing 3 to 4 applications over 2 days. SPECT/CT was used to assess the biodistribution. Follow up was performed clinically and with morphological imaging. Targeted radiopeptide therapy using 213Bi-DOTA-[Thi8, Met (O o)11]-Substanz P was very well tolerated by all patients. No additional neurological deficit was observed. Repetitive imaging is suggestive of progressive radiation-induced necrosis, which was validated by subsequent resection of the tumors. Time to progression was found to be 11 and 14 months respectively in patients with grade IV glioma. No progression is found after 18 to 23 months in patients with grade II or III glioma. We conclude that targeted loco-regional radiotherapy using 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P represents an innovative and effective treatment strategy for functionally critical located malignant gliomas. Primarily non operable gliomas may become resectable in the course of this treatment. We found a tendency towards a longer time to progression in 2 patients with grade IV glioma. (author)