Iodine-129 microdosing for protein and peptide drug development: erythropoietin as a case study

Background: Microdosing is a technique for studying the behavior of compounds in vivo at 1/100th of the dose of a test substance calculated, based on animal data, to yield a pharmacologic effect. In microdosing, use is made of accelerator MS (AMS). In this study, we investigated whether 129I-labeling of proteins with subsequent AMS measurements is a suitable method to perform microdose studies with therapeutic proteins. We used erythropoietin (EPO) as a case study. Results: In an animal study with 129I-labeled EPO in Han-Wistar rats, an increase of 129I-EPO is observed after dose administration. The half-life was found to be 2...