Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.
The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy.


METHODS
Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients.


RESULTS
This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival.


CONCLUSIONS
This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.
Akabani
Gamal
G
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
Reardon
David A
DA
Coleman
R Edward
RE
Wong
Terence Z
TZ
Metzler
Scott D
SD
Bowsher
James E
JE
Barboriak
Daniel P
DP
Provenzale
James M
JM
Greer
Kim L
KL
DeLong
David
D
Friedman
Henry S
HS
Friedman
Allan H
AH
Zhao
Xiao-Guang
XG
Pegram
Charles N
CN
McLendon
Roger E
RE
Bigner
Darell D
DD
Zalutsky
Michael R
MR
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy; D011874:Radiometry; D012086:Reoperation; D019063:Tenascin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin