• 15 December 1999
    • journal article
    • Vol. 59 (24), 6159-63
Abstract
Present day imaging of brain tumors requires a disrupted blood-brain barrier (BBB). However, the BBB is intact in the early stages of brain tumor growth, when diagnosis is most critical. Relative to normal brain, brain tumor cells frequently overexpress peptide receptors, such as the receptor for epidermal growth factor (EGF). Peptide radiopharmaceuticals such as radiolabeled EGF could be used to image early brain tumors, should these radiopharmaceuticals be made transportable through the BBB. The present studies describe a bifunctional molecule that contains both biologically active human EGF radiolabeled with 111In and an anti-transferrin receptor monoclonal antibody that undergoes transcytosis through the BBB via the endogenous transferrin transport system. The two domains of the bifunctional conjugate are separated by a Mr 3400 polyethyleneglycol linker, which releases steric hindrance and allows the conjugate to bind to both the EGF receptor, to image the brain tumor, and to the transferrin receptor, to enable transport through the BBB. Successful imaging of experimental brain tumors with this system is demonstrated in nude rats bearing cerebral implants of human U87 glioma.