Biological Models in Radiopharmaceutical Development, 1996 Developments in Nuclear Medicine Series, Vol. 27

Radiophannaceuticals labeled with short-lived radionuclides are utilized to unravel biochemical processes, and to diagnosis and treat diseases of the living body are-developed through extensive evaluation in ~iological models. 'fhC first attempt to compile information was a volume entitled ANIMAL MODELS IN RADIOTRACER DESIGN that was edited by William C. Eckelman and myself in 1983. The volume had a focus on the animal models that investigators were using in order to design radiotracers that displayed in vivo selectivity as measured by biodistribution and pharmacokinetic studies. A concern in the early days of nuclear medicine was species differences. Often a series of labeled compounds were evaluated in a several different animal models in order to gain confidence that the selected radiotracer would behave appropriately in humans. During the past 12 years there have been remarkable advances in molecular genetics, molecular biology, synthetic radiopharmaceutical chemistry, molecular modeling and visualization, and emission tomography. Biological models can now be selected that are better defined in terms of molecular aspects of the disease process. The development of high resolution PET and SPET for clinical applications facilitates the development of new radiopharmaceuticals by the use of models to quantitatively evaluate drug effects, and progression of disease, and hence to arrive at better diagnosis and treatments for animals and humans. With these advances there is an effective use of biological models, and the refinement of alternatives for the development of new radiophannaceuticals.

Introduction. Scope of the Work. Guidelines for Research with Animals. Moral and Ethical Considerations. Principles and Training Programs. Design of Candidate Radiopharmaceuticals. Identification of Clinical Need. Choice of Radionuclide. Screening Studies. Drug Development. Concept of Biological Models. In vitro Models. Choice of Biological Models. Species Variations. Transgenic Mice. Dogs and Kangaroos. Poison Arrow Frog. Giraffe. Tomographic Physiological Chemistry. ARG. SPET. PET. SIMS. Keyword Guide to Selection of Biological Models. References. Glossary of Abbreviations.

This comprehensive resource guide reflects an analysis of the world literature, for the period between 1983 and June, 1995. It provides a succinct overview of the current status of biological models that can facilitate advances in the development of drugs and radiopharmaceuticals. Guidelines for the use of animals in research are necessarily re-stated in this monograph, as well as brief remarks concerning alternatives. This is an indispensable resource for radiopharmaceutical scientists, pharmacists, physicians, veterinarians and other professionals involved in biomedical research, drug and radiopharmaceutical development.