Apoptotic abscess imaging with super(99m)Tc-HYNIC-rh-Annexin-V

• Published in: Nuclear medicine and biology 2010-01, Vol.37 (1), p.29-34
• Main Authors: Penn, David L, Kim, Christopher, Zhang, Kaijun, Mukherjee, Archana, Devakumar, Devadhas, Jungkind, Donald, Thakur, Mathew L
• Format: Article
• Language: English
• ISSN: 0969-8051
• DOI: 10.1016/j.nucmedbio.2009.08.011

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 super(99m)Tc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced super(99m)TcO sub(4) super(-) 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 37C. PMNs were then incubated with super(99m)Tc-HYNIC-AnxV and associated super(99m)Tc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of super(99m)Tc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of super(99m)Tc-HYNIC-AnxV was 84.9+/-8.11%. At 17 h, super(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). super(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