Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase.
Twenty-seven patients with brain glioma were scanned using 123I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment.
Kalofonos
H P
HP
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Pawlikowska
T R
TR
Hemingway
A
A
Courtenay-Luck
N
N
Dhokia
B
B
Snook
D
D
Sivolapenko
G B
GB
Hooker
G R
GR
McKenzie
C G
CG
Lavender
P J
PJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging* / Q000628:therapy; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D066246:ErbB Receptors; D000469:Alkaline Phosphatase