In vivo metabolism of I-123 labeled semisynthetic low density lipoproteins. Final technical report, September 28, 1988--September 27, 1990

摘要

We previously observed that small model beta-strand peptides (MBPs) selectively bind to human low density lipoprotein (hLDL) in vitro, and that some MBPs can be labeled with I-123-tyramine cellobiose (I-123-TyC). We hypothesized that metabolism of semisynthetic hLDL should mimic that of covalently labeled native hLDL, and planned to evaluate the biodistribution in rabbits of semisynthetic hLDL; to determine effects of prior oxidation and acetylation of the adsorbing hLDL on binding of MBPs and upon biodistribution of semisynthetic particles; and to begin biodistribution studies with semisynthetic hLDL in human subjects, with the eventual goal of application to experimental and clinical nuclear imaging studies. We have synthesized a radioiodotyrosine-containing MBP, designated betay, as a more suitable adsorbant to hLDL thanradioiodine-TyC-MBP, and optimized conditions for preparing radioiodine-betaY:hLDL. In rabbits both betaY and betaY:hLDL complexes were cleared from the bloodstream much more rapidly than radioiodine-TyC-hLDL or In-111-hLDL, and betaY in either form showed a biodistribution pattern different from that of directly radiolabeled hLDL. Even though radioiodine-betaY can be quickly and easily produced, we conclude that neither betaY alone nor semisynthetic betaY:hLDL particles are likely to prove useful as tracers of hLDL metabolism in vivo.