Abstract 5672: Detecting tissue susceptibility to celecoxib treatment using a whole-body imaging approach

Abstract Purpose: The goal of this study was to evaluate an in vivo imaging technique, which detects phospholipid membrane reorganization, as a molecular marker for tissue response induced by celecoxib as a canonical black box drug which is also being repurposed for anticancer treatment. Methods: 99mTc-duramycin was used as a phosphatidylethanolamine (PE)-binding imaging agent and was injected intravenously at 1 hour prior to imaging at designated time points. Sprague Dawley rats (male, 8-10 weeks) were treated with a single dose of 200 mg/kg or 1000 mg/kg celecoxib via oral gavage. A pilot study was conducted in duplicates with planar imaging on days 1, 3, 5 and 7 to determine the approximate window of signal changes, then whole-body single photon emission computed tomography (SPECT) was acquired for nontreated control, 200 mg/kg and 1000 mg/kg celecoxib-treated groups (n=12 per group). Blood and tissues from 4 animals in each group were collected for complete blood and serum panels and histopathology. The radioactivity uptake in tissues and organs were determined and statistically compared to the control group using unpaired t test. Results: The imaging data detected no significant changes with low dose (200 mg/kg) celecoxib treatment, but in a number of tissues/organs in high dose (1000 mg/kg) treatment, including the adipose tissue, blood, brain, upper right quadrant of the abdomen, heart, kidney, skeletal muscle, stomach, and testes. Histopathology analysis is ongoing to validate the imaging findings. Data from complete serum panel detected significantly elevated total protein, albumin and sodium. Conclusion: The study demonstrated the assessment of tissue susceptibility as a result of celecoxib treatment, which were consistent with known adverse effects of the drug. The current approach will be useful for detecting potential off-target side effects of anticancer treatments and drug candidates. Citation Format: Steven Johnson, Justin Jeffery, Jungwha Lee, Ming Zhao. Detecting tissue susceptibility to celecoxib treatment using a whole-body imaging approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5672.