Integrating Novel Imaging Technologies to Investigate Drug-Induced Kidney Toxicity

INTEGRATING NOVEL IMAGING TECHNOLOGIES TO INVESTIGATE DRUG-INDUCED KIDNEY TOXICITY 

Drug Discovery Toxicology From Target Assessment to Translational Biomarkers, First Edition. Edited by Y vonne Will, J. Eric McDuffie, Andrew J. Olaharski, and Brandon D. Jelly. 

Here we present and discuss a range of novel approaches combining emerging imaging technologies with detection of renal function in a range of animal models of induced kidney injury. It is anticipated that clinical translation is feasible in some cases with additional development. 

It had previously been shown that renal function could be estimated through the measurement of dye clearance in conscious mice. These studies have been based on traditional approaches where inulin and the related derivative fructosan sinistrin, as well as diethylenetriamine pentaace-tate (DTPA), have been used in various forms as renal clearance substances (Silkalns et al., 1973 Goates et al., 1990 Jung et al 1992 McLachlan et al 2001). Their detection involved enzymatic or colorimetric measurements of inulin and sinistrin from serum or urine or scintigraphy of radiolabeled DTPA. 

Recent advances in detecting renal function include the development of fluorescently labeled novel compounds (hydrophilic pyrazine dyes, carbostyril 124-DTPA-Eu, fluorescein-labeled poly-D-lysine) and their detection via in vivo fluorescence imaging or through transcutaneous detection (Dorshow et al., 1998 Rabito et al., 2005 Rajagopalan et al, 2011 Poreddy et al, 2012). Both the hydrophilic pyrazine dyes (see Fig. 34.1) and the modified DTPA are cleared exclusively by glomerular filiation, and 

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