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

## TL;DR

This study develops a new radiotracer, [99mTc]Tc-carvedilol, for non-invasive cardiac receptor imaging with high accuracy and selectivity.

## Contribution

The paper introduces a novel radiolabeled compound with improved cardiac uptake and stability for adrenoceptor quantification.

## Key findings

- [99mTc]Tc-carvedilol achieved 96.5% radiolabeling efficiency and >92% serum stability at 24 hours.
- Peak cardiac uptake in mice was 27.533% ID/g within 15 minutes, with minimal non-target tissue uptake.
- Docking analysis showed strong binding to β1-adrenoceptors with favorable pharmacokinetics compared to existing tracers.

## Abstract

Accurate 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.

[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.

[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.

The 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.

Schematic illustrating the study of Technetium-99m-labeled carvedilol as a cardiac imaging agent. The process includes reducing conditions, chemical structure, and biodistribution in mice with peak cardiac uptake. Comparative analysis shows advantages over other compounds. Docking analysis reveals stable binding to β1-adrenoceptors. An outcome diagram shows imaging results and emphasizes the potential for non-invasive cardiac diagnostics. A mouse is depicted in a scanning machine.