Evaluation of novel cationic Tc(I)-99m-tricarbonyl complexes as potential heart imaging agents

Abstract

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Objectives: To evaluate cationic complexes, [Tc-99m-(CO)3(L)]+ (L = N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L1), N-ethoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (PNP6), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L2) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L3)) as potential radiotracers for heart imaging.

Methods: Biodistribution studies were performed in Sprauge-Dawley rats. Planar images of the rats administered with 15±2 MBq of the radiotracer were obtained using a PhoGama large field-of-view Anger camera.

Results: Cationic complexes [Tc-99m-(CO)3(L)]+ (L = L1 - L3, and PNP6) were prepared with high radiochemical purity. Biodistribution data showed that the cationic complex [Tc-99m-(CO)3(L2)]+ has a high heart uptake, a long myocardial retention, and a rapid clearance from the liver. While its heart uptake and heart/lung ratios are comparable to those of Tc-99m-Sestamibi, its heart/liver ratio is 4-5 times better at 2 h postinjection. The heart uptake and heart/liver ratios of [Tc-99m-(CO)3(L2)]+ are comparable to those of Tc-99m-N-DBODC5 over the 2 h study period. [Tc-99m-(CO)3(L1)]+ has heart/liver ratios comparable to those of [Tc-99m-(CO)3(L2)]+; but its heart uptake is not as good. Planar imaging studies show that [Tc-99m-(CO)3(L1)]+ and [Tc-99m-(CO)3(L2)]+ have a faster rapid liver clearance than Tc-99m-Sestamibi. At 60 min postinjection, the liver activity almost disappeared for [Tc-99m-(CO)3(L1)]+ and [Tc-99m-(CO)3(L2)]+ while the liver activity of Tc--99m-Sestamibi remains high. The fast liver clearance suggests that [Tc-99m-(CO)3(L2)]+ might be able to give clinically useful diagnostic images of the heart as early as 30 min postinjection. A model compound [Re(CO)3(L4)]Br (L4=N,N-bis[(2-diphenylphosphino)ethyl]methoxyethylamine) has been prepared and characterized by elemental analysis, IR, ESI-MS, NMR (1H, 13C, 1H-1H COSY, and 1H-13C HMQC) methods, and X-ray crystallography. It was found that [Re(CO)3(L4)]+ is able to maintain its cationic nature with no dissociation of carbonyl ligands or any of the three PNP donors.

Conclusions: The cationic complex [Tc-99m-(CO)3(L2)]+ is a very promising radiotracer for myocardial perfusion imaging.

Comparison of the selected biodistribution data andT/B ratios at 2 h postinjection.