Imaging brain tumors by targeting peptide radiopharmaceuticals through theblood-brain barrier

Present day imaging of brain tumors requires a disrupted blood-brain barrie r (BBB). However, the BBB is intact in the early stages of brain tumor grow th, when diagnosis is most critical. Relative to normal brain, brain tumor cells frequently overexpress peptide receptors, such as the receptor for ep idermal growth factor (EGF). Peptide radiopharmaceuticals such as radiolabe led EGF could be used to image early brain tumors, should these radiopharma ceuticals be made transportable through the BBB. The present studies descri be a bifunctional molecule that contains both biologically active human EGF radiolabeled with In-111 and an anti-transferrin receptor monoclonal antib ody that undergoes transcytosis through the BBB via the endogenous transfer rin transport system. The two domains of the bifunctional conjugate are sep arated by a M-r 3400 polyethyleneglycol linker, which releases steric hindr ance and allows the conjugate to bind to both the EGF receptor, to image th e 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.