Inflammation and infection imaging with a Tc-99m-neutrophil elastase inhibitor in monkeys

A radiolabeled human neutrophil elastase inhibitor (EPI-HNE-2) may represen t an improved nuclear medicine imaging agent for inflammation and infection . This peptide displays rapid pharmacokinetics due to its low molecular wei ght and localizes specifically on neutrophil elastase released in inflammat ory sites by activated neutrophils. Methods: In this investigation, the pep tide was radiolabeled with Tc-99m using N-hydroxysuccinimidyl S-acetylmerca ptoacetyltriglycline (NHS-MAG(3)) as a bifunctional chelator and was admini stered on 18 occasions to 5 rhesus monkeys with inflammation/infection. Res ults: Plasma clearance was rapid, with liver and kidneys representing the m ajor organs of accumulation. No evidence of toxicity, dosage effects, or ci rculating antiMAG(3)-EPI-HHE-2 antibodies was observed. Specificity of loca lization was established using radiolabeled bovine pancreatic trypsin inhib itor (a non-hNE-binding peptide of similar size) as a nonspecific negative control peptide and by predosing with unlabeled EPI-HNE-2 to block receptor sites before the administration of radiolabeled EPI-HNE-2. The ability of radiolabeled EPI-HNE-2 to image inflammation/infection was evaluated in 12 studies in monkeys receiving only radiolabeled EPI-HNE-2 and with lesions i n the arm, shoulder, or lower back. Positive images were obtained in all st udies, uptake was apparent almost immediately, and images were still positi ve 24 h later. As a positive control, animals also received nonspecific IgG antibody radiolabeled with Tc-99m either directly or by NHS-MAG(3). Compar ed with labeled antibody, plasma clearance of Tc-99m was faster with labele d EPI-HNE-2 and accumulation in liver and heart was lower. Uptake of radioa ctivity in the inflammation was higher during the first hour with EPI-HNE-2 versus antibody but lower thereafter. Conclusion: When radiolabeled with T c-99m, EPI-HNE-2 localized specifically in inflammations in a monkey model and provided early images of diagnostic quality.