a) 201-Thallium chloride.
This is a potassium-analogue with active transport through the plasmatic membrane by means of the Na-K-ATPase pump. After intravenous administration, kinetics of 201Tl can be divided into two different phases: initial uptake and redistribution. Initial uptake depends on regional myocardial blood flow and extraction fraction, and the image at this stage represents myocardial perfusion. Myocardial concentration of 201Tl changes over time, which is known as redistribution, reaching an equilibrium with plasmatic concentration of the isotope. This phenomenon is evident when an initial perfusion defect is "filled in" or normalized in the late images hours after injection, which typically occurs under ischemic conditions. Late concentration of 201Tl is believed to represent integrity of cell membrane metabolic processes and thus, viability. Following this concept, four abnormal regional perfusion patterns can be defined: reversible perfusion defects, non-reversible defects, partially reversible defects and inverse or paradoxical reversibility. These patterns respectively represent ischemia, infarction and ischemia plus infarction, while inverse reversibility is still a controversial subject. Wash-out rate of 201Tl from the myocardium is also a useful functional parameter that can be measured with appropriate available software.
b) 99mTC- Isonitriles
Isonitriles are a group of cathionic liposoluble complexes designed as myocardial perfusion agents to be labelled with 99mTc, of which 6-methoxy-isobutyl-isonitrile (MIBI or sestamibi) is commercially available. As with 201 Tl, myocardial uptake of99mTc-MIBI is proportional to myocardial blood flow within a physiologic range. Extraction fraction is somewhat lower than that of 201Tl, underestimating high flows but being relatively higher at low flows. It enters the myocardial cell by passive diffusion and intracellular retention is prolonged, being trapped at the mithocondrial level with no significant redistribution. Experimental observations have demonstrated myocardial uptake even in the presence of severe metabolic alterations, however necrotic tissue does not exhibit retention of 99m Tc-MIBI so this should be considered not only a perfusion marker, but to some extent a viability agent too.
c) 99mTc-phosphines.
These are also cathionic lipophyllic agents, being tetrofosmin the only one commercially available. Several studies have demonstrated properties similar to those of 99mTc-MIBI regarding uptake and retention, although with more rapid hepatic clearance, allowing shorter acquisition waiting time after injection and slightly better dosimetry. Clinical efficacy in nuclear cardiology is totally similar to 99m Tc-MIBI, and technical protocols are almost identical.
d) Other radiopharmaceuticals.
Myocardial sympathetic innervation can be imaged with 123I-MIBG with applications in ischemic and non-ischemic heart disease. 99mTc-NOET is a perfusion agent with redistribution properties similar to those of thallium, not yet commercially available. Recently, nitroimidazoles labelled with 99mTc have been developed which accumulate in hypoxic tissues, giving a positive image of myocardial ischemia although still needing clinical validation. The process of apoptosis or programmed cell death has been successfully imaged experimentally with 99m Tc-annexin-V representing a promising and exciting new radiopharmaceutical with several potential clinical uses.
