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Peptide radiopharmaceuticals are potential imaging agents for brain disorders, should these agents be enabled to undergo transport through the blood-brain barrier (BBB) in vivo. Radiolabeled Abeta1-40 images brain amyloid in tissue sections of Alzheimer's disease autopsy brain, but this peptide radiopharmaceutical cannot be used to image brain amyloid in vivo owing to negligible transport through the BBB. In these studies, 125I-Abeta1-40 was monobiotinylated (bio) and conjugated to a BBB drug delivery and brain targeting system comprised of a complex of the 83-14 monoclonal antibody (mAb) to the human insulin receptor, which is tagged with streptavidin (SA). A marked increase in rhesus monkey brain uptake of the 125I-bio-Abeta1-40 was observed after conjugation to the 8314-SA delivery system at 3 h after intravenous injection. In contrast, no measurable brain uptake of 125I-bio-Abeta1-40 was observed in the absence of a BBB drug delivery system. The peptide radiopharmaceutical was degraded in brain with export of the iodide radioactivity, and by 48 h after intravenous injection, 90% of the radioactivity was cleared from the brain. In conclusion, these studies describe a methodology for BBB drug delivery and brain targeting of peptide radiopharmaceuticals that could be used for imaging amyloid or other brain disorders.

the journal of clinical investigation/the journal of clinical investigation

Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor.