Novel 99mTc(III) Complexes [99mTcCl(CDO)(CDOH)2B-R] (CDOH2 = Cyclohexanedione Dioxime) Useful as Radiotracers for Heart Imaging

Abstract

In this study, we evaluated seven new ^99mTc(III) complexes [^99mTcCl(CDO)(CDOH)₂B-R] (^99mTc-2Fboroxime: R = 2-formylfuran-3-yl (2F); ^99mTc-3Fboroxime: R = furan-3-yl (3F); ^99mTc-5Fboroxime: R = 5-formyfuran-2-yl (5F); ^99mTc-HPboroxime: R = 6-hydroxylpyridin-2-yl (HP); ^99mTc-MPYboroxime: R = 5-methoxypyridin-3-yl (MPY); ^99mTc-PMboroxime: R = 1,5-pyrimidin-3-yl (PM); and ^99mTc-4PYboroxime: R = pyridin-4-yl (4PY)) for their potential as heart imaging agents. All new ^99mTc(III) radiotracers except ^99mTc-2Fboroxime were prepared with high radiochemical purity (RCP > 95%). The low RCP (∼75%) for ^99mTc-2Fboroxime is most likely caused by steric hindrance from the 3-formyl group. Biodistribution and imaging studies were performed in SD rats. Planar image quantification was performed to compare their myocardial retention times. We found that the myocardial washout curves of new ^99mTc(III) radiotracers were best fitted the biexponential decay function. The AUC (area under the curve) values followed the general trend: ^99mTc-5Fboroxime (129 ± 6) > ^99mTc-3Fboroxime (114 ± 11) > ^99mTc-Teboroxime (104 ± 16) > ^99mTc-MPYboroxime (92 ± 18) > ^99mTc-4PYboroxime (77 ± 10) > ^99mTc-PMboroxime (68 ± 14) ≈ ^99mTc-HPboroxime (62 ± 14). The 2 min heart uptake values from biodistribution studies follow the ranking order of ^99mTc-5Fboroxime (3.75 ± 0.15%ID/g) ≈ ^99mTc-MPYboroxime (3.73 ± 0.24%ID/g) > ^99mTc-PMboroxime (3.47 ± 0.15%ID/g) ≈ ^99mTc-3Fboroxime ≈ (3.25 ± 0.77%ID/g). The 5 min heart uptake of ^99mTc-5Fboroxime (3.91 ± 0.09%ID/g) was almost identical to its 2 min heart uptake (3.75 ± 0.15%ID/g), and its 15 min heart uptake value (2.83 ± 0.08%ID/g) compared well to the 2 min heart uptake of ^99mTc-Teboroxime (3.00 ± 0.37%ID/g). It took ∼5 min for ^99mTc-5Fboroxime to approach the 1 min heart uptake value of ^99mTc-Teboroxime (∼3.5% ID/g) and ∼9.5 min to reach the 2 min heart uptake value of ^99mTc-Teboroxime (∼3.0% ID/g). The best image acquisition window is 0-5 min for ^99mTc-5Fboroxime. High-quality single-photon emission computed tomography images of the rat hearts were acquired in any of the 5 min window over the first 20 min after its administration. ^99mTc-5Fboroxime has significant advantages over ^99mTc-Teboroxime as the radiotracer for myocardial perfusion imaging.