ApoSense: A novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

Maya Damianovich, Ilan Ziv*, Samuel N. Heyman, Seymour Rosen, Ahuva Shina, Dvora Kidron, Tali Aloya, Hagit Grimberg, Galit Levin, Ayelet Reshef, Alfonso Bentolila, Avi Cohen, Anat Shirvan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)281-291
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume33
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Apoptosis imaging
  • Cell death detection
  • Renal disease
  • Renal uptake
  • Small animal imaging

Fingerprint

Dive into the research topics of 'ApoSense: A novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis'. Together they form a unique fingerprint.

Cite this