Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors.
Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing tumors, was administered intravenously to 12 patients with brain tumors. Six patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73 m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side-effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed antibody localization, with the best tumor delineation on single-photon emission tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake in the normal craniospinal axis was detected. There was no difference in the pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and time-activity curves based on quantitative imaging showed peak uptake in high-grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9 rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was agreement on positive sites when immunoscintigraphy was compared with technetium-99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium-201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken together, these data suggest that quantitative estimates of antibody targeting to intracranial tumors can be made using the modified conjugate view method.
Arbit
E
E
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA.
Cheung
N K
NK
Yeh
S D
SD
Daghighian
F
F
Zhang
J J
JJ
Cordon-Cardo
C
C
Pentlow
K
K
Canete
A
A
Finn
R
R
Larson
S M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002648:Child; D003847:Deoxyglucose / Q000031:analogs & derivatives; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D016719:Radioimmunodetection; D013400:Sugar Acids; D016284:Technetium Tc 99m Pentetate; D013794:Thallium Radioisotopes; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D013400:Sugar Acids; D013794:Thallium Radioisotopes; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; C100014:technetium Tc 99m gluceptate; D016284:Technetium Tc 99m Pentetate