Influence of Fluorine Substitution Pattern in Arylboronic Acid Caps on the Myocardial Perfusion Imaging Properties of Technetium Monocapped Tris(dioxime) Complexes

Abstract

Boronate-based myocardial perfusion tracers represent a promising scaffold for quantitative SPECT myocardial blood flow (MBF) imaging. In this study, five fluorinated 99mTc-labeled boronate derivatives were designed to systematically investigate the influence of fluorine substitution patterns on tracer pharmacokinetics and imaging performance. The fluorination pattern markedly influenced myocardial uptake, hepatic clearance, and overall biodistribution, with 99mTc-2F-HMPBA (99mTc-2F) and 99mTc-3F-HMPBA (99mTc-3F) exhibiting the most favorable profiles. Mechanistic evaluation using isolated heart perfusion demonstrated a high first-pass extraction fraction over a wide range of coronary flow rates, while dynamic SPECT imaging in swine showed tracer-derived K1 values comparable to 13N−NH3 PET-derived MBF. In particular, 99mTc-3F exhibited a more balanced pharmacokinetic profile with improved heart-to-liver contrast. These findings establish fluorine substitution as an effective strategy for tuning the pharmacokinetic behavior of boronate-based myocardial perfusion tracers and identify 99mTc-3F as a promising lead for quantitative SPECT myocardial perfusion imaging.