title: ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis.
abstract: OBJECTIVE
  Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia.
  
  
  METHODS
  Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis.
  
  
  RESULTS
  ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining.
  
  
  CONCLUSIONS
  ApoSense technology should have significant clinical utility for real-time, noninvasive detection of renal parenchymal damage of various types and evaluation of its distribution and magnitude; it may facilitate the assessment of efficacy of therapeutic interventions in a broad spectrum of disease states.
authors.affiliation: NeuroSurvival Technologies (NST) Ltd., 5 Odem St., Kiryat Matalon, Petah Tikva 49170, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Damianovich
authors.forename: Ilan
authors.initials: I
authors.lastname: Ziv
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Heyman
authors.forename: Seymour
authors.initials: S
authors.lastname: Rosen
authors.forename: Ahuva
authors.initials: A
authors.lastname: Shina
authors.forename: Dvora
authors.initials: D
authors.lastname: Kidron
authors.forename: Tali
authors.initials: T
authors.lastname: Aloya
authors.forename: Hagit
authors.initials: H
authors.lastname: Grimberg
authors.forename: Galit
authors.initials: G
authors.lastname: Levin
authors.forename: Ayelet
authors.initials: A
authors.lastname: Reshef
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bentolila
authors.forename: Avi
authors.initials: A
authors.lastname: Cohen
authors.forename: Anat
authors.initials: A
authors.lastname: Shirvan
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001709:Biotechnology / Q000379:methods; D003553:Cystine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003619:Dansyl Compounds / Q000493:pharmacokinetics; D005456:Fluorescent Dyes; D006801:Humans; D019169:Jurkat Cells; D007673:Kidney Cortex Necrosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
chemical_list: D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D019275:Radiopharmaceuticals; D014316:Tritium; C038494:di(dansyl)cystine; D003553:Cystine