DRUG TARGETING OF A PEPTIDE RADIOPHARMACEUTICAL THROUGH THE PRIMATE BLOOD-BRAIN-BARRIER IN-VIVO WITH A MONOCLONAL-ANTIBODY TO THE HUMAN INSULIN-RECEPTOR

Peptide radiopharmaceuticals are potential imaging agents for brain di sorders, should these agents be enabled to undergo transport through t he blood-brain barrier (BBB) in vivo. Radiolabeled A beta(1-40) images brain amyloid in tissue sections of Alzheimer's disease autopsy brain , but this peptide radiopharmaceutical cannot be used to image brain a myloid in vivo owing to negligible transport through the BBB. In these studies, I-125-A beta(1-40) was monobiotinylated (bio) and conjugated to a BBB drug delivery and brain targeting system comprised of a comp lex of the 83-14 monoclonal antibody (mAb) to the human insulin recept or, which is tagged with streptavidin (SA). A marked increase in rhesu s monkey brain uptake of the I-125-bio-A beta(1-40) was observed after conjugation to the 8314-SA delivery system at 3 h after intravenous i njection. In contrast, no measurable brain uptake of I-125-bio-A beta( 1-40) was observed in the absence of a BBB drug delivery system. The p eptide radiopharmaceutical was degraded in brain with export of the io dide radioactivity, and by 48 h after intravenous injection, 90% of th e radioactivity was cleared from the brain. In conclusion, these studi es describe a methodology for BBB drug delivery and brain targeting of peptide radiopharmaceuticals that could be used for imaging amyloid o r other brain disorders.