c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies.
ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product.
Bakir
M A
MA
Joint Department of Physics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Eccles
S
S
Babich
J W
JW
Aftab
N
N
Styles
J
J
Dean
C J
CJ
Lambrecht
R M
RM
Ott
R J
RJ
Eccles
S A
SA
Styles
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016719:Radioimmunodetection / Q000379:methods*; D051381:Rats; D014055:Tomography, Emission-Computed; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins