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

Mary Rusckowski, Tong Qu, James M. Pullman, Robin Marcel, Arthur C. Ley, Robert C. Ladner, Donald J. Hnatowich

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A radiolabeled human neutrophil elastase inhibitor (EPI-HNE-2) may represent an improved nuclear medicine imaging agent for inflammation and infection. This peptide displays rapid pharmacokinetics due to its low molecular weight and localizes specifically on neutrophil elastase released in inflammatory sites by activated neutrophils. Methods: In this investigation, the peptide was radiolabeled with 99mTc using N- hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) as a bifunctional chelator and was administered on 18 occasions to 5 rhesus monkeys with inflammation/infection. Results: Plasma clearance was rapid, with liver and kidneys representing the major organs of accumulation. No evidence of toxicity, dosage effects, or circulating antiMAG3-EPI-HNE-2 antibodies was observed. Specificity of localization was established using radiolabeled bovine pancreatic trypsin inhibitor (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 in the arm, shoulder, or lower back. Positive images were obtained in all studies, uptake was apparent almost immediately, and images were still positive 24 h later. As a positive control, animals also received nonspecific IgG antibody radiolabeled with 99mTc either directly or by NHS-MAG3. Compared with labeled antibody, plasma clearance of 99mTc was faster with labeled EPI-HNE-2 and accumulation in liver and heart was lower. Uptake of radioactivity in the inflammation was higher during the first hour with EPI-HNE-2 versus antibody but lower thereafter. Conclusion: When radiolabeled with 99mTc, EPI-HNE-2 localized specifically in inflammations in a monkey model and provided early images of diagnostic quality.

Original languageEnglish (US)
Pages (from-to)363-374
Number of pages12
JournalJournal of Nuclear Medicine
Volume41
Issue number2
StatePublished - Feb 2000
Externally publishedYes

Fingerprint

Secretory Proteinase Inhibitory Proteins
Haplorhini
Inflammation
Infection
Peptides
Antibodies
Leukocyte Elastase
Aprotinin
Liver
Nuclear Medicine
Chelating Agents
Macaca mulatta
Radioactivity
Neutrophils
Arm
Pharmacokinetics
Immunoglobulin G
Molecular Weight
Kidney

Keywords

  • Tc-peptide
  • Inflammation and infection imaging

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Rusckowski, M., Qu, T., Pullman, J. M., Marcel, R., Ley, A. C., Ladner, R. C., & Hnatowich, D. J. (2000). Inflammation and infection imaging with a 99mTC-neutrophil elastase inhibitor in monkeys. Journal of Nuclear Medicine, 41(2), 363-374.

Inflammation and infection imaging with a 99mTC-neutrophil elastase inhibitor in monkeys. / Rusckowski, Mary; Qu, Tong; Pullman, James M.; Marcel, Robin; Ley, Arthur C.; Ladner, Robert C.; Hnatowich, Donald J.

In: Journal of Nuclear Medicine, Vol. 41, No. 2, 02.2000, p. 363-374.

Research output: Contribution to journalArticle

Rusckowski, M, Qu, T, Pullman, JM, Marcel, R, Ley, AC, Ladner, RC & Hnatowich, DJ 2000, 'Inflammation and infection imaging with a 99mTC-neutrophil elastase inhibitor in monkeys', Journal of Nuclear Medicine, vol. 41, no. 2, pp. 363-374.
Rusckowski, Mary ; Qu, Tong ; Pullman, James M. ; Marcel, Robin ; Ley, Arthur C. ; Ladner, Robert C. ; Hnatowich, Donald J. / Inflammation and infection imaging with a 99mTC-neutrophil elastase inhibitor in monkeys. In: Journal of Nuclear Medicine. 2000 ; Vol. 41, No. 2. pp. 363-374.
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