The application of the radiopharmaceutical was straightforward. The radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient. The observation period ranged from 7 to 66 months after completion of targeted radiopeptide therapy. Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation of the tumor.

In addition to the preclinical and clinical evaluation of DOTATAGA-SP, a more sophisticated dosimetry protocol was applied to this novel therapy option (Kneifel et al. 2007). The aim was to establish a reproducible dosimetry for intratumoral radiopeptide therapy to be able to compare the doses of this modality to external beam radiotherapy and to identify the effective dose range. In 12 patients with malignant gliomas 2 MBq of ¹¹¹In-substance P and 370–3,330 MBq of ⁹⁰Y-substance P were applied subsequently, and each time serial SPECT scans were acquired over a period of 24 h. Quantitative voxelwise dose distribution maps (in Gy/GBq) were computed from these data. The correlation between pre- and post-therapeutic dosimetry was accurate. The calculated absorbed dose to the tumor was found to be as high as 40–483 Gy/GBq (mean 155 Gy/GBq) for the first therapeutic injection with ⁹⁰Y-substance P. Given an average therapeutic activity of 30 mCi (1.11 GBq) this results in a mean absorbed radiation dose of 172 Gy within the tumor.

Based on these encouraging results two further studies were initiated with radiolabeled SP.

First of all it was analyzed whether neoadjuvant treatment prior to tumor resection is also a valid concept to improve therapy of malignant brain tumors (Cordier et al. 2010). The previous study (Kneifel et al. 2006) showed, that from a surgical point of view, resectability was facilitated due to improved demarcation and the radiation-induced anti-angiogenic effect in these patients who had been treated upfront with loco-regional radiopeptide therapy.

A total of 17 glioblastoma (GBM) patients were treated by local injection of ⁹⁰Y-DOTAGA-substance P prior to tumor resection. Patients were treated by four cycles of intracavitary radiopeptide therapy with ⁹⁰Y-DOTAGA-substance P in monthly intervals. In case of suspected tumor recurrence on imaging studies, confirmation or exclusion by biopsy was offered. The cumulative injected activity ranged from 100 to 345 mCi. A summary of the therapy scheme as well as the results of this study is given in Table 2.