Synthesis and biological evaluation of ¹²⁵I-nebivolol as a potential cardioselective agent for imaging β₁-adrenoceptors

The aim of this study was to develop a potential selective radiopharmaceutical for the non-invasive assessment of cardiac β₁-adrenoceptors in vivo. Nebivolol is a cardioselective β₁-adrenergic receptor antagonist that was successfully labeled with NCA ¹²⁵I via direct electrophilic substitution at ambient temperature. The reaction parameters studied were nebivolol concentration, pH of the reaction mixture and kinds of oxidizing agents. The radiolabeled compound maintained its stability throughout working period of 24 h. In vivo uptake of ¹²⁵I-nebivolol in the heart was 8.51 ± 0.01% ID/organ at 0.5 h post-injection, whereas the clearance pathways from the rats appear to proceed via the hepatobiliary and renal clearance. Administration of cold nebivolol reduced the heart uptake to 2.1 ± 0.13% and further confirms the high specificity and selectivity of this radiotracer for the myocardial β₁-adrenoceptors.