The
adenosine A2B receptor has been proposed as a novel therapeutic target in
cancer, as its expression is drastically elevated in several
tumors and
cancer cells. Noninvasive molecular imaging via positron emission tomography (PET) would allow the in vivo quantification of this receptor in
pathological processes and most likely enable the identification and clinical monitoring of respective
cancer therapies. On the basis of a bicyclic pyridopyrimidine-2,4-dione core structure, the new
adenosine A2B receptor ligand 9 was synthesized, containing a
2-fluoropyridine moiety suitable for labeling with the short-lived PET
radionuclide fluorine-18. Compound 9 showed a high binding affinity for the human A2B receptor (Ki(A2B) = 2.51 nM), along with high selectivities versus the A1, A2A, and A3 receptor subtypes. Therefore, it was radiofluorinated via nucleophilic aromatic substitution of the corresponding nitro precursor using [18F]F-/K2.2.2./
K2CO3 in
DMSO at 120 °C. Metabolic studies of [18F]9 in mice revealed about 60% of radiotracer intact in plasma at 30 minutes p.i. A preliminary PET study in healthy mice showed an overall biodistribution of [18F]9, corresponding to the known ubiquitous but low expression of the A2B receptor. Consequently, [18F]9 represents a novel PET radiotracer with high affinity and selectivity toward the
adenosine A2B receptor and a suitable in vivo profile. Subsequent studies are envisaged to investigate the applicability of [18F]9 to detect alterations in the receptor density in certain
cancer-related disease models.