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Journal of Biomedical Optics • Open Access

Single-dose safety and pharmacokinetic evaluation of fluorocoxib A: pilot study of novel cyclooxygenase-2-targeted optical imaging agent in a canine model
Author(s): Maria Cekanova; Md. Jashim Uddin; Alfred Legendre; Gina Galyon; Joseph W. Bartges; Amanda Callens; Tomas Martin-Jimenez; Lawrence J. Marnett

Paper Abstract

We evaluated preclinical single-dose safety, pharmacokinetic properties, and specific uptake of the new optical imaging agent fluorocoxib A in dogs. Fluorocoxib A, N-[(5-carboxy-X-rhodaminyl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, selectively binds and inhibits the cyclooxygenase-2 (COX-2) enzyme, which is overexpressed in many cancers. Safety pilot studies were performed in research dogs following intravenous (i.v.) administration of 0.1 and 1  mg/kg fluorocoxib A. Blood and urine samples collected three days after administration of each dose of fluorocoxib A revealed no evidence of toxicity, and no clinically relevant adverse events were noted on physical examination of exposed dogs over that time period. Pharmacokinetic parameters were assessed in additional research dogs from plasma collected at several time points after i.v. administration of fluorocoxib A using high-performance liquid chromatography analysis. The pharmacokinetic studies using 1  mg/kg showed a peak of fluorocoxib A (92±28  ng) in plasma collected at 0.5 h. Tumor specific uptake of fluorocoxib A was demonstrated using a dog diagnosed with colorectal cancer expressing COX-2. Our data support the safe single-dose administration and in vivo efficacy of fluorocoxib A, suggesting a high potential for successful translation to clinical use as an imaging agent for improved tumor detection in humans.

Paper Details

Date Published: 1 November 2012
PDF: 11 pages
J. Biomed. Opt. 17(11) 116002 doi: 10.1117/1.JBO.17.11.116002
Published in: Journal of Biomedical Optics Volume 17, Issue 11
Show Author Affiliations
Maria Cekanova, The Univ. of Tennessee (United States)
Md. Jashim Uddin, Vanderbilt Univ. (United States)
Alfred Legendre, The Univ. of Tennessee (United States)
Gina Galyon, The Univ. of Tennessee (United States)
Joseph W. Bartges, The Univ. of Tennessee (United States)
Amanda Callens, The Univ. of Tennessee (United States)
Tomas Martin-Jimenez, The Univ. of Tennessee (United States)
Lawrence J. Marnett, Vanderbilt Univ. (United States)


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