99mTc hexakis-t-butyl isonitrile (TBI): an agent for the diagnosis of coronary artery diseases.

Basic and clinical studies were undertaken to determine pharmacokinetic mechanisms, blood flow-related characteristics and potential clinical utility of the 99mTc hexakis-t-butyl isonitrile (TBI) in the non-invasive diagnosis of ischemic heart diseases. Pharmacokinetic studies with TBI in animals demonstrated a high initial lung, heart and liver uptake. The lung clears at a relatively faster rate, the activity in the heart remained constant with a buildup of activity in the liver. These pharmacokinetic characteristics allowed for a myocardial imaging at 30-45 min post-injection at rest. The regional myocardial distribution of TBI was shown to be linearly related to microsphere-determined regional myocardial blood flow with a redistribution potential in transient ischemic myocardium (i.e., mimics 201Tl). The first pass extraction fraction (in vitro) for TBI was shown to be nearly 100% and independent on flow levels. In general, the slow tissue clearance rate or the lack of it might be due to the high degree of lipophilicity with the complete lack of any hepatic or extrahepatic metabolism to a less lipophilic metabolite. The complex demonstrated a high degree of cardiac membrane association. The net extraction in isolated heart slices was shown to be dependent on pH and temperature, independent of energy. The clinical studies demonstrated a similar pharmacokinetic pattern to the animal studies and documented the perfusion and ventricular function utility of TBI in the diagnosis of ischemic heart diseases.