99mTc-technetium labeling of antiarthritic peptides to evaluate homing and biodistribution at inflamed joints

PurposeThe 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.ProcedureNε-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of 99mTc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with 99mTc. 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.ResultsGamma scintigraphy imaging showed that the biodistribution of all 99mTc-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.ConclusionsThis study highlights the versatility of using the His derivative linker for 99mTc 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.