BIOLOGICAL DISTRIBUTION OF TC-99M-LABELED YIGSR AND IKVAV LAMININ PEPTIDES IN RODENTS - TC-99M-IKVAV PEPTIDE LOCALIZES TO THE LUNG

Two laminin-derived peptides containing either YIGSR or IKVAV (single amino acid code) sequences were radiolabeled with Tc-99m and their bio logical distribution evaluated in rodents. Both Tc-99m-peptides cleare d rapidly from the circulation though the kidney, and to a lesser exte nt, through the liver. Tc-99m-YIGSR peptide did not accumulate in any organ examined in normal, tumored, and emphysemic mice. The Tc-99m-IKV AV peptide localized within 10 min to the lung of normal animals, resu lting in lung-to-blood ratios of approximately 23: 1. The 99mTc-IKVAV peptide localized to lung after submicron filtration and after intrape ritoneal injection, suggesting that particulates do not play a major r ole in localization. Pre-incubation of Tc-99m-IKVAV peptide in whole b lood decreased lung localization, suggesting that margination of radio labeled blood cells does not play a major role in the lung localizatio n. When Tc-99m-IKVAV was injected into mice with tumored lungs (melano ma), the lung uptake was markedly increased (up to 20% injected dose h igher than control lungs) at all time points examined (10, 30, and 120 min). When Tc-99m-IKVAV was injected into mice with genetic emphysema , the lung uptake was markedly decreased at all time points. The local ization of the Tc-99m-IKVAV-containing peptide to the lung is consiste nt with a receptor-based mechanism.