Regional Pharmacokinetics of Orally Administered PET Tracers

Abstract

Positron emission tomography (PET) is currently the most useful imaging technique for noninvasive measurement of drug pharmacokinetics regionally in a variety of tissues. Over the past decade, PET measurements have provided many critical insights about the tissue distribution of several classes of drugs; neuroleptics, antimicrobials, antineoplastics, etc. PET measurements can be performed after any route of drug administration, intravenous, inhalation or oral, however, intravenously administered drugs have been the most extensively evaluated. Studies of orally administered drugs are clearly of great interest; however, formulation issues have precluded widespread applications in these areas. In this report, we discuss the unique problems associated with studying orally administered drugs and review the results of recent studies performed in our laboratory.

Positron Emission Tomography: Applications In Drug Discovery and Drug Development

“…The labeled active compound can be called a ligand, a tracer, or a probe. To ensure an adequate signal during imaging, tracer synthesis should not only yield products with sufficient substitution of the stable atom by its positronemitting isotopes, but the radiolabeling, purification, and formulation must be completed within 3 half-lives of the radionuclide [16]. Since the half-lives of most PET isotopes are in minutes, this makes labeling a particularly demanding part of PET imaging.…”

“…Hence, a PET synthesis and imaging facility must be located near a cyclotron. Tracer synthesis should be done within 3 half-lives of the radionuclide [16] and imaging should take place within 1 or 2 half-lives after the completion of the synthesis [14]. A PET tracer should have the desirable pharmacokinetics so it can be imaged within a short period of time.…”

Introduction on PET: Description of Basics and Principles

“…Second, if the test drug itself can be labeled with a positron emitter, PET may be employed to study the pharmacokinetics of a novel drug candidate. After intravenous injection, inhalation or ingestion of the labeled compound, the time-dependent concentration of radioactivity in different organs and tissues can be measured quantitatively (Klimas, 2002;Hutchinson et al, 2003;Fischman et al, 2000;Berridge et al, 2000) (see Fig. 4).…”