Basic, Translational, and Clinical Research for Radionuclide Therapy of Human Glioma
The combination strategy for the treatment of the front wave of tumor invasion in brain tumors using 211At-labeled anti-tenascin chimeric 81C6, Combretastatin A1-P (OxiGene, Inc.) and the vascular permeability modifier Cereport® (Alkermes, Inc.) is being studied in a rat-brain animal model using GFP-D566 human glioma cells. This strategy consists of interrupting the pathophysiology of tumor growth and invasion at different spatio-temporal points. Using MR microscopy, microPET and histopathology analysis, Drs. Gamal Akabani-Hneide, Darell D. Bigner, and Michael Zalutsky are studying the patterns of cell invasion and the overall effect of this strategy.
A Phase II clinical trial based on the treatment of new and recurrent brain tumor patients with a fixed absorbed dose of 44 Gy to the 2-cm cavity margins using 131I-labeled murine 81C6 mAb is currently undergoing in the Neuro-Oncology Program. The objective is to determine the median survival and toxicity, and compare these results with those obtained from previous clinical protocols that are based only on administered activity. The hypothesis is that a targeted dose of 44 Gy will result in a median survival equal or higher than that obtained using only a fixed administered activity (MTD) and that the incidence of acute and delayed neurotoxicity will be lower in these patients. Therefore, the researchers have calculated the resulting treatment plan in these patients based on cavity size and residence time and obtained the three-dimensional distribution of the radiolabeled mAb using single photon computed tomography (SPECT), which was co-registered with MRI images, in order to assess absorbed doses (iso-contours) to the different regions of the brain. This analysis was carried out for further use and comparison with subsequent MR studies (longitudinal study) for the assessment of tumor progression and neurological toxicity analysis, including radionecrosis. The relevance of these calculations are now being appreciated, as these dosimetric results are being requested by other hospitals and institutions where patients are being treated with external beam therapy and included as an overall treatment strategy.