Development of a Radiofluorinated Adenosine A_2B Receptor Antagonist as Potential Ligand for PET Imaging

Area of Science:

• Molecular Imaging
• Radiochemistry
• Pharmacology

Background:

• Adenosine A2B receptor is upregulated in various cancers, presenting a potential therapeutic target.
• Positron Emission Tomography (PET) enables in vivo quantification for cancer therapy monitoring.
• Development of selective radiotracers is crucial for noninvasive molecular imaging.

Purpose of the Study:

• To synthesize and characterize a novel PET radiotracer targeting the adenosine A2B receptor.
• To evaluate the binding affinity, selectivity, and in vivo properties of the new radiotracer.
• To assess the potential of the radiotracer for cancer imaging and monitoring.

Main Methods:

• Synthesis of a novel adenosine A2B receptor ligand (compound 9) based on a pyridopyrimidine-2,4-dione core.
• Radiofluorination of compound 9 using [18F]fluoride for PET imaging.
• In vitro binding assays to determine affinity and selectivity for adenosine receptor subtypes.
• In vivo metabolic and biodistribution studies in mice using the radiotracer [18F]9.

Main Results:

• Compound 9 exhibited high binding affinity (Ki(A2B) = 2.51 nM) and selectivity for the human A2B receptor over other subtypes.
• [18F]9 was successfully synthesized with good radiochemical yield.
• Metabolic studies showed approximately 60% of intact radiotracer in mouse plasma at 30 minutes post-injection.
• Preliminary PET studies in mice indicated a biodistribution pattern consistent with known A2B receptor expression.

Conclusions:

• [18F]9 is a novel PET radiotracer with high affinity and selectivity for the adenosine A2B receptor.
• The radiotracer possesses a suitable in vivo profile for molecular imaging applications.
• Further studies are warranted to evaluate [18F]9 in cancer models for detecting receptor density alterations.