125I-labeled OP-1 is locally retained in a rabbit lumbar fusion model

Osteogenic protein-1 is evolving as a potential bone graft alternative. Surgical site retention is important to maximize local osteoinduction and to limit peripheral effects. An established rabbit lumbar posterolateral fusion model was used to evaluate the systemic distribution and pharmacokinetics of locally applied osteogenic protein-1 delivered on a collagen carrier. L5-L6 intertransverse process fusions were performed on 27 New Zealand White rabbits. Radiolabeled (125)I-osteogenic protein-1 collagen putty was implanted. At intervals, whole blood, plasma, and excreta were analyzed for radioactivity with liquid scintillation counting. Surgical site and tissue radioactivity also were assessed by quantitative whole-body autoradioluminography of animals euthanized at times ranging from 6 hours to 35 days. Animals remaining at the final time were assessed for fusion with manual palpation, radiography, and histology. Limited distribution of radioactivity was observed in the blood, plasma, and tissues apart from at the surgical site and in the urinary bladder and thyroid. The mean residence time for osteogenic protein-1 collagen putty was 10.4 +/- 2.7 days. These excretion profiles and kinetic properties are similar to those described for recombinant human bone morphogenetic protein-2 in the rabbit model (mean residence times of 7.6 days and 10.2 days with different carriers).