PT  - JOURNAL ARTICLE
AU  - David A. Reardon
AU  - Jennifer A. Quinn
AU  - Gamal Akabani
AU  - R. Edward Coleman
AU  - Allan H. Friedman
AU  - Henry S. Friedman
AU  - James E. Herndon II
AU  - Roger E. McLendon
AU  - Charles N. Pegram
AU  - James M. Provenzale
AU  - Jeannette M. Dowell
AU  - Jeremy N. Rich
AU  - James J. Vredenburgh
AU  - Annick Desjardins
AU  - John H. Sampson
AU  - Sridharan Gururangan
AU  - Terence Z. Wong
AU  - Michael A. Badruddoja
AU  - Xiao-Guang Zhao
AU  - Darell D. Bigner
AU  - Michael R. Zalutsky
TI  - Novel Human IgG2b/Murine Chimeric Antitenascin Monoclonal Antibody Construct Radiolabeled with <sup>131</sup>I and Administered into the Surgically Created Resection Cavity of Patients with Malignant Glioma: Phase I Trial Results
DP  - 2006 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 912--918
VI  - 47
IP  - 6
4099  - http://jnm.snmjournals.org/content/47/6/912.short
4100  - http://jnm.snmjournals.org/content/47/6/912.full
SO  - J Nucl Med2006 Jun 01; 47
AB  - Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of 131I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. Methods: In this phase I trial, eligible patients received a single injection of 131I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). 131I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after 131I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. Results: We treated 47 patients with 131I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. Conclusion: The MTD of 131I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, 131I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with 131I-murine 81C6.