ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosisReport as inadecuate




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European Journal of Nuclear Medicine and Molecular Imaging

, Volume 33, Issue 3, pp 281–291

First Online: 29 November 2005Received: 15 March 2005Accepted: 04 July 2005

Abstract

PurposeAcute 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.

MethodsUsing 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.

ResultsApoSense 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.

ConclusionApoSense 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.

KeywordsApoptosis imaging Cell death detection Renal disease Renal uptake Small animal imaging M. Damianovich and I. Ziv had an equal contribution to the paper.

Potential conflict of interest: ApoSense is a product developed by NST, Ltd. NST financially supported the research presented in full. M. Damianovich, I. Ziv, T. Aloya, H. Grimberg, G. Levin, A. Reshef, A. Bentolila, A. Cohen, and A. Shirvan are NST employees. S.N. Heyman, S. Rosen , A. Shina, and D. Kidron have no actual or potential conflict of interest in relation to this article. ApoSense is still an investigational product.

An erratum to this article is available at http:-dx.doi.org-10.1007-s00259-011-1961-3.

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Author: Maya Damianovich - Ilan Ziv - Samuel N. Heyman - Seymour Rosen - Ahuva Shina - Dvora Kidron - Tali Aloya - Hagit Grimberg

Source: https://link.springer.com/



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