Nuclear Imaging in Drug Development — Introduction

Abstract

The use of radioactive isotopes to generate images has developed in many directions to yield a series of sophisticated technologies with numerous applications in drug discovery and development. Imaging techniques now allow precise quantitative measurements to be made with high spatial resolution and ever improving time resolution. This brief introductory review will illustrate some of the practical applications of this technology to pharmaceutical research, using examples from our own laboratory which focuses on drug discovery and development in the CNS area. Repeated reference will be made to the applications of nuclear imaging to studies of the compound dizocilpine (1, MK-801), an antagonist of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. This compound was first discovered as a novel anticonvulsant agent in our US laboratories more than a decade ago (Clineschmidt et al., 1982) and was later found to act as a potent noncompetitive NMDA antagonist (Wong et al., 1986). It has been found to be a powerful neuroprotective agent in a number of animal models of cerebral ischemia, which suggests the potential of NMDA antagonists for use in human cerebral ischemia, e.g., in the acute treatment of stroke (Iversen et al., 1989).