Receptor Mapping PET Studies

Receptor studies use radioligands—chemicals incorporating a positron-emitting isotope into a molecule whose pharmacokinetics are already known. Ideally, these ligands bind specifically to one receptor type. Most of these studies are of the mapping type, which shows the distribution of a particular receptor in the brain (e.g., dopamine type 2 [D2] receptor). Here, the measured radioactivity reflects both the local concentration of receptors (Bmax) and the affinity of the ligand for the receptor (measured by Kd, the equilibrium dissociation constant). If the ligand acts as a competitive antagonist, then the apparent affinity is also affected by the concentration of the endogenous neurotransmitter. The analysis can be simplified by considering the ratio of Bmax to Kd, termed the binding potential (BP). Ligands undergo both specific and nonspecific binding. Typically, one is interested only in the specific binding (i.e., to the receptor of interest). Use of a reference tissue that is known to have a low receptor concentration allows one to subtract out the nonspecific binding (e.g., the cerebellum has a low concentration of D2 receptors). In this case, the difference in distribution for the two tissues is directly proportional to the BP. Ligands require a more involved synthesis than either water or 18FDG, and their use is a race against the clock as the isotope decays. The end product must meet several requirements: high specific activity (amount of radioactivity per mole), high radiochemical purity, and sterility. 18F ligands are easier to synthesize because of their long half-life, but 11C ligands (20-minute half-life) have a higher potential for biological relevance. These will be discussed in the next section, which addresses psychopharmacological applications of PET tracers and ligands.

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