The localization of human breast carcinomas by radiolabelled monoclonal antibodies.
Immune-deprived mice bearing HX99 human breast carcinoma xenografts were injected with a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to investigate the dependence of tumour localization on (i) tumour site and (ii) antibody radiolabel. No significant difference was found in the degree of localization of radio-iodinated M8 in subcutaneous, renal or intracranial xenografts, but a highly significant improvement in HX99 localization by M8 was recorded using an 111indium-DTPA conjugate of the antibody (111In-DTPA-M8), related to its rapid tumour uptake and blood pool clearance. Radio-iodinated or 111In-labelled M8 was given to 29 patients with breast cancer, 7 with primary tumours and 22 with metastases. Tumour localization was assessed by (i) examination of surgical specimens and (ii) antibody scans, which were compared with conventional X-rays and 99mTc-methylene diphosphonate (MDP) bone scans. Radiolabelled M8 localized preferentially in all primary tumours (radioactivity tumour: normal breast = 6.2 +/- 1.4 [mean +/- s.e.]). All ten patients with skeletal metastases had positive 111In-DTPA-M8 scans, but the correlation with X-rays and MDP scans showed a regional variation. Radio-iodinated M8 failed to identify metastases in any site. The favourable biodistribution of 111In-DTPA-M8 has led to the clear localization of breast carcinomas in patients and mice. In future such reagents may rationalize the clinical management of breast cancer.
D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D004164:Diphosphonates; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007204:Indium; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D004369:Pentetic Acid; D011859:Radiography; D011868:Radioisotopes; D011877:Radionuclide Imaging; D012588:Scintillation Counting; D013667:Technetium; D013669:Technetium Tc 99m Medronate; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D004164:Diphosphonates; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D007204:Indium; D013667:Technetium; D004369:Pentetic Acid; D013669:Technetium Tc 99m Medronate