Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V.
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.
Penn
David L
DL
Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Kim
Christopher
C
Zhang
Kaijun
K
Mukherjee
Archana
A
Devakumar
Devadhas
D
Jungkind
Donald
D
Thakur
Mathew L
ML
D000038:Abscess / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism / Q000493:pharmacokinetics; D017209:Apoptosis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
D017304:Annexin A5; D015609:Organotechnetium Compounds; D011994:Recombinant Proteins; C515698:technetium Tc 99m hydrazinonicotinamide-annexin V