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

• Published in: Nuclear medicine and biology Vol. 37; no. 1; pp. 29 - 34
• Main Authors: Penn, David L., Kim, Christopher, Zhang, Kaijun, Mukherjee, Archana, Devakumar, Devadhas, Jungkind, Donald, Thakur, Mathew L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2010; Elsevier
• Subjects: 99mTc-HYNIC-rh-Annexin-V; Abscess - diagnostic imaging; Abscess - immunology; Abscess - metabolism; Abscess - pathology; Animals; Annexin A5 - metabolism; Annexin A5 - pharmacokinetics; Apoptosis; Apoptotic abscess imaging; Bacterial diseases; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Human bacterial diseases; Humans; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mice; Mice, Inbred BALB C; Miscellaneous; Miscellaneous. Technology; Neutrophils - cytology; Neutrophils - metabolism; Organotechnetium Compounds - metabolism; Organotechnetium Compounds - pharmacokinetics; Pharmacology. Drug treatments; Polymorphonuclear leukocytes; Radionuclide Imaging; Radionuclide investigations; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacokinetics; Tissue Distribution; Polymorphonuclear leukocytes; Apoptotic abscess imaging; 99mTc-HYNIC-rh-Annexin-V; Radionuclide study; Human; Nuclear medicine; Radiolabelling; Rodentia; Abscess; Inflammation; Differential diagnostic; Infection; Vertebrata; Mammalia; Mouse; Animal; Technetium 99mTc; Tc-HYNIC-rh-Annexin-V; Bacteriosis; Neutrophil; Technique; Phosphatidylserine; Labelled compound; Apoptosis
• ISSN: 0969-8051; 1872-9614; 1872-9614
• 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 99mTc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced 99mTcO 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°C. PMNs were then incubated with 99mTc-HYNIC-AnxV and associated 99mTc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of 99mTc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of 99mTc-HYNIC-AnxV was 84.9±8.11%. At 17 h, 99mTc-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). 99mTc-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≤.05) and 24 h ( P≤.01). 99mTc-HYNIC-AnxV represents a minimally invasive and promising agent to image and potentially distinguish between infectious and inflammatory abscesses.