Selective COX-2 radioligands for PET imaging of neuroinflammation

This technology is a group of fluorine radioisotopes that can be used to quantify cyclooxygenase-2 (COX-2) induction via PET imaging.

Unmet Need: Non-invasive molecular imaging method for quantifying COX-2 induction

Cyclooxygenase-2 (COX-2) is an enzyme whose activity is upregulated during injury, inflammation, and cellular proliferation. COX-2 overactivation has been implicated in cancer, pain pathogenesis, and neuroinflammation in various neurological diseases. While monitoring changes in COX-2 induction would provide a versatile diagnostic tool, existing approaches have been limited by the suboptimal pharmacology and physiological properties of the radioligands. Noninvasive functional brain imaging (e.g., PET) of specified radiolabeled protein markers of inflammation would be a powerful tool for disease diagnostics.

The Technology: High-affinity selective COX-2 inhibitor used for quantifying COX-2 induction

This technology describes [¹⁸F] fluorine-labeled high-affinity selective COX-2 inhibitors, which can be used for quantifying COX-2 induction using PET imaging. The synthetic radioligands, [¹⁸F]FMTP and [¹⁸F]TMI, have a superior affinity to COX-2 compared to celecoxib, a validated COX-2 inhibitor. Furthermore, unlike conventional ¹¹C-labeled ligands, [¹⁸F]-labeled tracers can be conveniently synthesized and distributed from the manufacturing site to multiple diagnostic centers. This technology may provide a non-invasive molecular imaging method for the quantification of COX-2 induction, thus providing more efficient diagnostics for diseases that involve neuroinflammation and the upregulation of COX-2.

The efficacy of these radiotracers for PET imaging has been demonstrated in a mouse model of neuroinflammation.

Applications:

• PET imaging of COX-2-mediated neuroinflammation
• Synthetization of radiolabeled compounds
• Monitoring processes and diseases that involve the upregulation of COX-2 protein expression
• Measurement of inflammation markers expression levels and distribution
• Differential diagnosis of inflammatory, neurological, and neurodegenerative diseases
• Use in targeting radiotherapy for cancer treatment

Advantages:

• Features an array of radiolabeled compounds
• Can be used in cell culture, mammalian animal models, and humans
• Applicable to various disease models, including inflammatory, pulmonary, cardiovascular, urogenital, and neoplastic disease
• Superior affinity compared to existing tracers
• Easily synthesized
• Long half-life
• Non-invasive
• Cost-effective

Lead Inventor:

J. John Mann, M.D.

Patent Information:

Patent Pending (US20220106275)

Related Publications:

• Kumar JSD, Prabhakaran J, Molotkov A, Sattiraju A, Kim J, Doubrovin M, Mann JJ, Mintz A. “Radiosynthesis and evaluation of [¹⁸F]FMTP, a COX-2 PET ligand.” Pharmacol Rep. 2020 Oct; 72(5): 1433-40.

• Kumar D, Zanderigo F, Prabhakaran J, Rubin-Falcone H, Parsey RV, Mann JJ. “In vivo evaluation of [¹¹C] TMI, a cox-2 selective PET Tracer, in baboons.” Bioorg Med Chem Lett. 2018 Dec 15; 28(23-24): 3592-3595.

• Prabhakaran J, Underwood M, Zanderigo F, Simpson NR, Cooper AR, Matthew J, Rubin-Falcone H, Parsey RV, Mann JJ, Kumar D. “Radiosynthesis and in vivo evaluation of [¹¹C]MOV as a PET imaging agent for COX-2.” Bioorg Med Chem Lett. 2018 Aug 1; 28(14): 2432 2435.

Tech Ventures Reference:

• IR CU19254

• Licensing Contact: Jerry Kokoshka