99mTc-3Cboroxime: a novel 99mTc(iii) complex [99mTcCl(CDO)(CDOH)2B-3C] (CDOH2 = cyclohexanedione dioxime; 3C-B(OH)2 = 3-(carbamoylphenyl)boronic acid) with high heart uptake and long myocardial retention

Abstract

In this study, a new ^99mTc(III) complex [^99mTcCl(CDO)(CDOH)₂B-3C] (^99mTc-3Cboroxime: CDOH₂ = cyclohexanedione dioxime; 3C-B(OH)₂ = 3-(carbamoylphenyl)boronic acid) was evaluated as a radiotracer for heart imaging. ^99mTc-3Cboroxime was prepared in high radiochemical purity (RCP > 95%). Biodistribution and imaging studies were performed using Sprague–Dawley rats (200–225 g). We found that the heart uptake of ^99mTc-3Cboroxime (3.43 ± 0.11%ID g⁻¹) at 2 min postinjection (p.i.) was close to that of ^99mTc-Teboroxime (3.00 ± 0.37%ID g⁻¹), and the heart uptake value of ^99mTc-3Cboroxime was almost unchanged over the first 15 min (3.05 ± 0.35%ID g⁻¹ at 15 min p.i.). ^99mTc-3Cboroxime had lower uptake than ^99mTc-Teboroxime in the blood, lungs and muscle over a 60 min period. Its heart/blood, heart/lung and heart/muscle ratios were better than those of ^99mTc-Teboroxime. These results suggest that ^99mTc-3Cboroxime has a significant advantage over ^99mTc-Teboroxime with respect to myocardial retention and heart/background ratios. However, its liver uptake at 2 min p.i. was higher than that of ^99mTc-Teboroxime. Because of its faster liver clearance, ^99mTc-3Cboroxime had heart/liver ratios close to or better than that of ^99mTc-Teboroxime at ≥5 min p.i. As a result, good quality SPECT images could be obtained in any of the 5 min imaging windows over the first 20 min after injection of ^99mTc-3Cboroxime. More importantly, the results from this study show that the use of the 3-carbamylphenyl group is an interesting approach to achieve long heart retention for new ^99mTc(III) radiotracers. Future research will focus on further minimizing liver radioactivity while maintaining high heart uptake over a wide time window.