Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging

• Type of Material: Article
• Authors: Elizabeth De Jesus, University of Pennsylvania; Jane J. Keating, University of Pennsylvania; Sumith A. Kularatne, On Target Laboratories, Inc.; Jack Jiang, University of Pennsylvania; Ryan Judy, University of Pennsylvania; Jarrod Predina, University of Pennsylvania; Shuming Nie, Emory University; Philip Low, Purdue University; Sunil Singhal, University of Pennsylvania
• Language: English
• Date: 2015
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Elizabeth De Jesus et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1155/2015/469047
• Title of Journal or Parent Work: International Journal of Molecular Imaging
• ISSN: 2090-1712
• Volume: 2015
• Start Page: 1
• End Page: 10
• Grant/Funding Information: This work was supported by the National Institutes of Health R01 CA163256-01 (Sunil Singhal and Shuming Nie).
• Research Categories: Chemistry, General; Health Sciences, Medicine and Surgery; Engineering, Biomedical

Abstract

Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (p < 0.001). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48–5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes.