Aβ1-40 peptide radiopharmaceuticals could be used to image Aβ brain amyloid in transgenic mouse models of Alzheimer's disease should the Aβ peptide radiopharmaceutical be made transportable through the blood-brain barrier (BBB) in vivo. The present studies used the R17-217 rat monoclonal antibody to the mouse transferrin receptor as a BBB drug targeting vector for the delivery to brain of Aβ1-40 radiolabeled with either 125-Iodine or 111-Indium. The Aβ peptide radiopharmaceutical is conjugated to the R17 MAb using avidin biotin technology, wherein the Aβ1-40 peptide radiopharmaceutical is monobiotinylated (bio) and bound to a conjugate of the R17 MAb and streptavidin (SA). The [125I]-bio-Aβ1-40 or the [111In]-bio-Aβ1-40 either free or bound to the R17/SA conjugate was injected intravenously into anesthetized adult mice and plasma pharmacokinetics and organ uptake were measured over the next 60 minutes. The Aβ1-40 peptide radiopharmaceutical radiolabeled with 111-Indium was the preferred formulation, compared to peptide labeled with 125-Iodine, because there was a greater metabolic stability and reduced artifactual organ uptake of metabolites associated with the use of the 111-Indium nuclide. However, biotinylated Aβ1-40 peptide radiopharmaceuticals conjugated to the R17/SA brain drug targeting system were metabolically unstable in mice in vivo owing to active biotinidase activity. Future work involving brain drug targeting in mice that utilizes avidin biotin technology will need to incorporate biotin analogues that are resistant to biotinidase.
Bibliographical noteFunding Information:
This work is supported by the U.S. Department of Energy. Daniel Jeong skillfully prepared the manu- script.