Pharmacokinetic characterization of fluorocoxib D, a cyclooxygenase-2-targeted optical imaging agent for detection of cancer.

Abstract

SIGNIFICANCE:

Fluorocoxib D, N-[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, is a water-soluble optical imaging agent to detect cyclooxygenase-2 (COX-2)-expressing cancer cells.

AIM:

We evaluated the pharmacokinetic and safety properties of fluorocoxib D and its ability to detect cancer cells in vitro and in vivo.

APPROACH:

Pharmacokinetic parameters of fluorocoxib D were assessed from plasma collected at designated time points after intravenous administration of 1  mg  /  kg fluorocoxib D in six research dogs using a high-performance liquid chromatography analysis. Safety of fluorocoxib D was assessed for 3 days after its administration using physical assessment, complete blood count, serum chemistry profile, and complete urinalysis in six research dogs. The ability of fluorocoxib D to detect COX-2-expressing cancer cells was performed using human 5637 cells in vitro and during rhinoscopy evaluation of specific fluorocoxib D uptake by canine cancer cells in vivo.

RESULTS:

No evidence of toxicity and no clinically relevant adverse events were noted in dogs. Peak concentration of fluorocoxib D (114.8  ±  50.5  ng  /  ml) was detected in plasma collected at 0.5 h after its administration. Pretreatment of celecoxib blocked specific uptake of fluorocoxib D in COX-2-expressing human 5637 cancer cells. Fluorocoxib D uptake was detected in histology-confirmed COX-2-expressing head and neck cancer during rhinoscopy in a client-owned dog in vivo. Specific tumor-to-normal tissue ratio of detected fluorocoxib D signal was in an average of 3.7  ±  0.9 using Image J analysis.

CONCLUSIONS:

Our results suggest that fluorocoxib D is a safe optical imaging agent used for detection of COX-2-expressing cancers and their margins during image-guided minimally invasive biopsy and surgical procedures.

• Authors: Maria Cekanova, Sony Pandey, Shelly Olin, Phillip Ryan, Jennifer E Stokes, Silke Hecht, Tomas Martin-Jimenez, Md Jashim Uddin, Lawrence J Marnett
• Journal: Journal of biomedical optics (J Biomed Opt) Vol. 25 Issue 8 (08 2020) ISSN: 1560-2281 [Electronic] United States
• PMID: 32860356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase 2

Topics

• Animals
• Antineoplastic Agents
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Dogs
• Neoplasms (diagnostic imaging)
• Optical Imaging