Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V.

Abstract

Abscess formation causes systemic and localized up-regulation of neutrophil [polymorphonuclear leukocytes (PMNs)] signaling pathways. In the abscess, following bacterial ingestion or PMN activation by inflammatory mediators, PMN apoptosis is elevated and leads to the externalization of phosphatidylserine. Annexin-V (AnxV) has been shown to have high affinity to externalized phosphatidylserine. We hypothesized that (99m)Tc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced (99m)TcO(4)(-) and its purity was determined by instant thin-layer chromatography. Apoptosis was induced in isolated human PMNs by incubation in 2% saline for 17 and 22 h at 37 degrees C. PMNs were then incubated with (99m)Tc-HYNIC-AnxV and associated (99m)Tc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of (99m)Tc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of (99m)Tc-HYNIC-AnxV was 84.9+/-8.11%. At 17 h, (99m)Tc-HYNIC-AnxV bound to apoptotic PMNs was 71.6+/-0.01% and 48.6+/-0.01% for experimental and control cells, respectively (P=.002). At 22 h, experimental cells retained 74.9+/-0.02% and control cells retained 47.2+/-0.02% (P=.005). (99m)Tc-HYNIC-AnxV associated with bacterial abscesses was 1.25+/-0.09 and 3.75+/-0.83 percent injected dose per gram (%ID/g) at 4 and 24 h compared to turpentine abscesses which was 1.02+/-0.16 and 0.72+/-0.17 %ID/g at 4 (P<or=.05) and 24 h (P<or=.01). (99m)Tc-HYNIC-AnxV represents a minimally invasive and promising agent to image and potentially distinguish between infectious and inflammatory abscesses.

• Authors: David L Penn, Christopher Kim, Kaijun Zhang, Archana Mukherjee, Devadhas Devakumar, Donald Jungkind, Mathew L Thakur
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 37 Issue 1 Pg. 29-34 (Jan 2010) ISSN: 1872-9614 [Electronic] United States
• PMID: 20122665 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Annexin A5
• Organotechnetium Compounds
• Recombinant Proteins
• technetium Tc 99m hydrazinonicotinamide-annexin V

Topics

• Abscess (diagnostic imaging, immunology, metabolism, pathology)
• Animals
• Annexin A5 (metabolism, pharmacokinetics)
• Apoptosis
• Humans
• Mice
• Mice, Inbred BALB C
• Neutrophils (cytology, metabolism)
• Organotechnetium Compounds (metabolism, pharmacokinetics)
• Radionuclide Imaging
• Recombinant Proteins (chemistry, metabolism, pharmacokinetics)
• Tissue Distribution