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Proceedings Paper

Drug toxicity assessment using label-free multimodal nonlinear optical imaging (Conference Presentation)

Paper Abstract

Pre-clinical toxicology is a statutory requirement of drug development and plays a significant role in reducing attrition in drug discovery. Histopathology and indirect methods such as measurement of toxicity-associated systemic markers in blood or urine samples are the state-of-the-art techniques for toxicity evaluation. Further improvements over these conventional techniques are needed to detect signs of drug-induced toxicity at earlier stages with higher sensitivity and specificity. Multiphoton nonlinear imaging techniques such as two-/three-photon microscopy (2PF/3PF), fluorescence lifetime imaging microscopy (FLIM), second/third harmonic generation (SHG/THG) and coherent anti-Stokes Raman scattering (CARS) microscopy can extract complimentary structural and metabolic information of the target tissue in a label-free manner. In this study, we investigated the capability of a multimodal multiphoton microscopy technique (2PF/3PF/SHG/THG/FLIM/CARS) for detecting both functional and structural changes associated with drug-induced toxicity. Cisplatin, a platinum-based chemotherapy drug, is a cytotoxic agent used to treat many types of cancers. Common side effects of Cisplatin include nephrotoxicity and gonadal dysfunction. We obtained multimodal optical images of organs such as kidney, liver, and testis harvested from mice treated with a single dose of Cisplatin (3mg/kg) by intraperitoneal injection. A control group was treated with 0.9% saline. Structural and metabolic biomarkers related to Cisplatin-induced toxicity were identified and characterized from these multimodal optical images obtained ex vivo. The preliminary results suggest that it may be possible to develop a novel platform for drug toxicity identification and assessment based on multimodal nonlinear optical imaging techniques.

Paper Details

Date Published: 4 March 2019
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Proc. SPIE 10859, Visualizing and Quantifying Drug Distribution in Tissue III, 108590I (4 March 2019); doi: 10.1117/12.2510032
Show Author Affiliations
Aneesh Alex, GlaxoSmithKline (United States)
Jang Hyuk Lee, Beckman Institute for Advanced Science and Technology, Univ. of Illinois (United States)
Jose J. Rico-Jimenez, Beckman Institute for Advanced Science and Technology, Univ. of Illinois (United States)
Eric J. Chaney, Beckman Institute for Advanced Science and Technology, Univ. of Illinois (United States)
Sunish Mohanan, GlaxoSmithKline (United States)
Stephen A. Boppart, Beckman Institute for Advanced Science and Technology, Univ. of Illinois (United States)
Steve R. Hood, GlaxoSmithKline (United Kingdom)


Published in SPIE Proceedings Vol. 10859:
Visualizing and Quantifying Drug Distribution in Tissue III
Kin Foong Chan; Conor L. Evans, Editor(s)

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