Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy.
OBJECTIVE
The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgically created resection cavities (SCRCs).


METHODS
Absorbed doses to the 2-cm-thick shell as measured from the margins of the resection cavity interface were estimated for 42 patients with primary brain tumors. MR images were used to assess the enhanced-rim volume as a function of time after radiolabeled MAb therapy. Biopsy samples 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, radionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I study, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimated average absorbed dose and initial dose rate to the 2-cm shell were 41 [9-89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreement 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 considerably and mainly depended on cavity volume. In future clinical trials, the administered activity of (131)I-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rather than giving a fixed administered activity.
Akabani
G
G
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. akaba001@mc.duke.edu
Cokgor
I
I
Coleman
R E
RE
González Trotter
D
D
Wong
T Z
TZ
Friedman
H S
HS
Friedman
A H
AH
Garcia-Turner
A
A
Herndon
J E
JE
DeLong
D
D
McLendon
R E
RE
Zhao
X G
XG
Pegram
C N
CN
Provenzale
J M
JM
Bigner
D D
DD
Zalutsky
M R
MR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D019063:Tenascin / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin