Use of PET Radiopharmaceuticals to Probe Cardiac Receptors

Receptors form a class of intrinsic membrane glycoproteins characterized by the high affinity and specificity with which they bind ligands. Receptors are associated directly or indirectly with membrane ion channels, which open or close after a conformational change of the receptor induced by the binding of the neurotransmitter or of an agonist to the specific site. In heart disease, alterations in receptor density, distribution, and subtypes have been widely demonstrated from samples collected by endomyocardial biopsy, during surgery, or at autopsy. Positron emission tomography (PET) now offers the unique possibility of determining in vivo the receptor density in humans. These measurements are based on the synthesis of a radioligand, usually a selective receptor antagonist labeled with a positron-emitting radioisotope such as 11C or 18F. Mathematical compartmental models applied to time-concentration curves obtained during saturation or displacement experiments can provide the values of the myocardial receptor density and of the rate constants of the ligand-receptor interaction. Several receptor classes have been characterized in human heart: beta- and alpha-adrenergic, muscarinic cholinergic, and peripheral-type benzodiazepine. PET can give information on changes in receptor number that are associated with different physiological and pathological processes. Noticeable progress in this field has emerged recently.