Tri-methoxy-tris-pyrazolyl-Tc-(CO)

Tri-methoxy-tris-pyrazolyl-Tc-(CO), abbreviated as Tc-TMEOP, is a radiotracer synthesized by Goethals et al. for myocardial perfusion imaging with single-photon emission computed tomography (SPECT) or planar imaging (1). Myocardial perfusion imaging is widely used to assess the blood flow to myocardium during periods of exercise (or stress) and rest (3-5). To precisely assess the blood flow, diverse compounds labeled with various radionuclides have been synthesized and tested in animals and in the clinic (2, 6). Basically, two major issues have to be considered when designing a radiotracer for perfusion imaging. The first issues to be considered are the flow-extraction rate and heart uptake (1, 2). The first-pass myocardial extraction fraction and heart uptake should be high enough to produce a strong signal for myocardial imaging. Both parameters are also essential to obtain high heart/liver, heart/lung, and heart/blood signal ratios at the early time point after injection of the radiotracers. Currently, most radiotracers are labeled with Tc, have a first-pass extraction fraction from 29% to 90%, show a heart uptake from 1% to 3% injected dose (ID), and display a myocardial signal proportional to the regional myocardial blood flow (2). However, some tracers can underestimate the blood flow in the high flow ranges (>2 mL.g−·min−) and overestimate the blood flow in the low flow ranges (<0.2 mL.g−·min−) (2, 4). The second issues to be considered are the liver uptake and clearance, which can significantly influence the diagnostic specificity of myocardial ischemia. Unfortunately, most Tc-labeled radiotracers suffer from high liver uptake with slow clearance, which leads to a high percentage of false-positive or negative results for myocardial ischemia, especially for ischemia in the inferior wall of heart (1). Stimulating patients by eating fatty food before imaging can reduce the liver signal, but the results can vary significantly between individual patients. An optimal radiotracer should have less liver uptake but fast clearance from liver. To overcome the problem of high liver uptake, Goethals et al. synthesized a new radiotracer, Tc-TMEOP, based on tri-carbonyl chemistry (1). TMEOP is a neutral and tridentate nitrogen donor chelator that forms a moderately lipophilic cationic complex upon reaction with the organometallic precursor fac-[Tc(OH)(CO)]. The investigators evaluated the in vitro properties and in vivo pharmacokinetics of Tc-TMEOP and compared them with the data obtained with Tc-sestamibi and Tc-tetrofosmin, two radiotracers approved for clinical use by the United States Food and Drug Administration (1). The results showed that Tc-TMEOP uptake in the heart was between those of Tc-sestamibi and Tc-tetrofosmin, but Tc-TMEOP exhibited a faster liver washout (1). This chapter summarizes the data obtained with Tc-TMEOP.