Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action.
Advances in positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS), and the ability to label a wide variety of compounds for in vivo use in humans, have created a new technology for making precise physiological and pharmacological measurements. Due to the noninvasive nature of these approaches, repetitive and/or continuous measurements have become possible. Thus far, these techniques have been primarily used for one-time assessments of individuals. However, experience suggests that a major use of this technology will be in the evaluation of new drug therapies. Already, these techniques have been used to measure precisely and noninvasively the pharmacokinetics of a variety of antimicrobial, antineoplastic and CNS agents. In the case of CNS drugs, imaging techniques (particularly PET) have been used to define the classes of neuroreceptors with which the drug interacts. The physiological, pharmacological and biochemical measurements that can be performed noninvasively using modern imaging techniques can greatly facilitate the evaluation of new therapies. These measurements are most likely to be useful during drug development in preclinical studies and in phase I/II human studies. Preclinically, new drugs can be precisely compared with standard therapies, or a series of analogues can be screened for further development on the basis of performance in animal models. In Phase I/II, imaging measurements can be combined with classical pharmacokinetic data to establish optimal administration schedules, evaluate the utility of interventions in specific clinical situations, and aid in the design of Phase III trials.
Fischman
Alan J
AJ
Department of Radiology, Division of Nuclear Medicine, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, USA.
Alpert
Nathaniel M
NM
Rubin
Robert H
RH
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002491:Central Nervous System Agents / Q000493:pharmacokinetics; D004341:Drug Evaluation; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation*; D009682:Magnetic Resonance Spectroscopy; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002491:Central Nervous System Agents; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals