William L. Rumsey

Potential of Nitroimidazoles as Markers of Hypoxia in Heart

It is well known that cardiac muscle has a high and continuous requirement for oxygen. Oxygen is primarily needed, i.e., over 95%, to maintain flux through mitochondrial oxidative phosphorylation for synthesis of ATP. Oxygen is delivered to the working cardiac myocytes at levels consistent with the prevailing metabolic demands established by the various ATP-dependent reactions, principally cycling of the contractile myofilaments. When oxygen delivery is diminished, for example during ischemia, electron flux within the respiratory chain is impeded by the lack of appropriate electron acceptor at the cytochrome oxidase reaction. Consequently, the concentration of reducing equivalents (NADH and FADH2) increases. This condition establishes the opportunity for these and other sources of biological reductants to interact with exogenously supplied molecules having high electron affinity.

[99mTc]teboroxime and [99mTc]Cl(DMG)3B2MP: Binding characteristics and metabolism of two [99mTc]BATOs in blood and tissues

Studies were performed in vitro and in vivo to evaluate the binding properties and metabolism of [99mTc]Cl(CDO)3BMe (Teboroxime) and [99mTc]Cl(DMG)3B2MP in blood and target tissues of rats. Both radiopharmaceuticals displayed rapid binding (within 1-3 min) with high affinity to plasma proteins and blood cells. The amounts of radioactivity associated with blood components became progressively greater with time of exposure to either compound. There was a higher proportion of the radiopharmaceuticals associated with blood components during in vivo conditions, likely due, at least in part, to clearance of the free fraction from the plasma pool. Exposure of both compounds to blood results in axial ligand exchange of the chloro atom to a hydroxyl. The results suggest that it is the free species that is extracted primarily by tissues.

Detecting Hypoxia in Heart Using Phosphorescence Quenching and 99MTechnetium-Nitroimidazoles

The oxygen requirements of cardiac muscle are high and continuous, due largely to the energy expended during cycling of contractile proteins. Any decrease in oxygen flow to the cardiac myocytes places these cells at risk for loss of function or possibly infarction dependent upon the duration of oxygen deprivation. It is well recognized therefore that a non-invasive method for evaluating the oxygenation state of the heart would be a valuable tool for both the research and the clinical setting.