AUTHOR=Azhari Hala F. 

TITLE=From radiolabeling to receptor quantification: preclinical assessment of [99mTc]Tc-carvedilol as a cardiac β-adrenoceptor probe

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1581598

DOI=10.3389/fphar.2025.1581598

ISSN=1663-9812

ABSTRACT=IntroductionAccurate cardiac adrenoceptor assessment is crucial for managing cardiovascular diseases. This study introduces a novel radiotracer, technetium-99m-labeled carvedilol ([99mTc]Tc-carvedilol), which advances non-invasive cardiac receptor evaluation by improving traceability and myocardial tissue selectivity. Aimed at strengthening diagnostic precision, it optimizes a selective radioligand for quantifying cardiac adrenergic receptor sites.Methods[99mTc]Tc-carvedilol was synthesized via direct radiolabeling with technetium-99m, key parameters were optimized to maximize radiolabeling efficiency and ensure a reliable and reproducible [99mTc]Tc-carvedilol complex. Biodistribution was rigorously evaluated in vitro and in vivo, emphasizing cardiac uptake, receptor occupancy, biodistribution, and clearance kinetics. Comparative analysis with [131I]iodocarvedilol and 99mTc-sestamibi provided insights into advancements in detection efficiency and translational potential.Results[99mTc]Tc-carvedilol showed a radiolabeling efficiency of 96.5% ± 2.87%, with serum stability >92% at 24 h. Biodistribution studies in Swiss Albino mice (24 mice, aged 10–12 weeks, weighing 25 ± 3 g) revealed peak cardiac uptake (27.533% ± 0.931% injected dose per Gram of tissue (ID/g) within 15 min post-injection, alongside efficient blood clearance and minimal non-target tissue uptake (5.972% ± 0.131% ID/g organ) by 120 min. Docking analysis confirmed robust β1-adrenoceptors (−9.2 kcal/mol) via hydrogen bonds and hydrophobic and electrostatic interactions. Compared to [131I]iodocarvedilol and 99mTc-sestamibi [99mTc]Tc-carvedilol exhibited superior stability, targeting accuracy, and pharmacokinetics.DiscussionThe enhanced selective cardiac uptake and favorable pharmacokinetics of [99mTc]Tc-carvedilol position it as a promising agent for non-invasive cardiac receptor mapping, with the potential to improve diagnostic accuracy and specificity. Further clinical validation is essential to confirm its efficacy in detecting and evaluating cardiac pathologies.