Dosimetry and dose-response relationships in newly diagnosed patients withmalignant gliomas treated with iodine-131-labeled anti-tenascin monoclonalantibody 81C6 therapy

Purpose: The objective of this study was to perform the dosimetry and evalu ate the dose-response relationships in newly diagnosed patients with malign ant brain tumors treated by direct injections of I-131-labeled 81C6 monoclo nal antibody (MAb) into surgically created resection cavities (SCRCs). Methods and Materials: Absorbed doses to the 2-cm-thick shell as measured f rom the margins of the resection cavity interface were estimated for 42 pat ients with primary brain tumors. MR images were used to assess the enhanced -rim volume as a function of time after radiolabeled MAb therapy. Biopsy sa mples were obtained from 15 patients and 1 autopsy. Results: The average absorbed dose [range] to the 2-cm shell region was 32 [3-59] Gy. For the endpoint of minimal time to MR contrast enhancement, the optimal absorbed dose and initial dose-rate were 43 +/- 16 Gy and 0.41 +/- 0.10 Gy/h, respectively. There was a correlation between the absorbed dose and dose rate to the shell region and biopsy outcome (tumor recurrence, ra dionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I st udy, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimat ed average absorbed dose and initial dose rate to the 2-cm shell mere 41 [9 -89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreem ent with the optimal values based on the time to MR lesion rim enhancement. Conclusions: The average absorbed dose to the 2-cm shell region varied cons iderably and mainly depended on cavity volume. In future clinical trials, t he administered activity of I-131-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rathe r than giving a fixed administered activity. (C) 2000 Elsevier Science Inc.