PURPOSE: The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis. PROCEDURE: N(ε)-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of (99m)Tc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with (99m)Tc. Peptides were purified by high-performance liquid chromatography, characterized by mass spectrometry, radiolabeled and injected into normal and arthritic rats to determine biodistribution and localization. RESULTS: Gamma scintigraphy imaging showed that the biodistribution of all (99m)Tc-labeled peptides were higher in the arthritic joints compared with the normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h postinjection) and attributed to increased blood flow to inflammatory sites. HAP-1 and CP-HAP-1 showed a greater uptake and localization to arthritic joints compared with controls. There was no difference in the physiological biodistribution of these agents in the heart, kidneys and the bladder. CONCLUSIONS: This study highlights the versatility of using the His derivative linker for (99m)Tc tagging of a variety of peptides. It also demonstrates greater peptide localization and thereby bioavailability of therapeutic peptides to inflamed joints following specific conjugation to homing peptides. The ability to localize peptide/drugs to inflamed synovium has important therapeutic implications.
PURPOSE: The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis. PROCEDURE: N(ε)-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of (99m)Tc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with (99m)Tc. Peptides were purified by high-performance liquid chromatography, characterized by mass spectrometry, radiolabeled and injected into normal and arthritic rats to determine biodistribution and localization. RESULTS: Gamma scintigraphy imaging showed that the biodistribution of all (99m)Tc-labeled peptides were higher in the arthritic joints compared with the normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h postinjection) and attributed to increased blood flow to inflammatory sites. HAP-1 and CP-HAP-1 showed a greater uptake and localization to arthritic joints compared with controls. There was no difference in the physiological biodistribution of these agents in the heart, kidneys and the bladder. CONCLUSIONS: This study highlights the versatility of using the His derivative linker for (99m)Tc tagging of a variety of peptides. It also demonstrates greater peptide localization and thereby bioavailability of therapeutic peptides to inflamed joints following specific conjugation to homing peptides. The ability to localize peptide/drugs to inflamed synovium has important therapeutic implications.