This study provides proof of concept that targeted local radiotherapy using (213)Bi-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.

Purpose: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid 125 I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. Experimental Design: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg 1 of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC 50 of 0.88 F 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, 90

The standard treatment of meningiomas is surgery or radiotherapy. Complex, especially recurrent or progressive cases, may exhibit tumor growth involving critical neurovascular structures or diffuse growth, resulting in limited efficacy and higher risk of standard treatment. We evaluated whether somatostatin receptor-targeted radionuclide therapy with 90 Y-DOTATOC may be a therapeutic option. Methods: Fifteen patients with recurrent or progressive meningiomas after multimodal pretreatment or unfavorable medical risk profile were treated with systemic 90 Y-DOTATOC. Endpoints were progression-free survival and toxicity. Results: Usually applied doses were 7,400 MBq/m 2 of 90 Y-DOTATOC in 2 fractions. Mean observation time was 49.7 mo (range, 12-137 mo). Overall median progression-free survival was at least 24 mo. Toxicity was moderate, mostly hematologic (n 5 8) and transient. Conclusion: 90 Y-DOTATOC therapy is feasible and may represent a promising second-or third-line option for complex meningiomas, which are progressive or otherwise not treatable with a reasonable risk-benefit ratio.

No abstract

Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevant.