In the past. I have symbolized molecular nuclear medicine as the apex of a triangle with genetics and pharmacology iii the base. Inside the triangle is tile expression "Imaging regional function and biochemistry." Few fields of science have created the excitement and promise of tile human genome program, an international collaborative effort that promises not only to revolutionize biology but also he translated into a whole new way of looking at health care.
Since its inception nearly 50 years ago, nuclear medicine has been molecular m its orientation, and clearly plays a major role in biomedical imaging, not only in human beings but also in experimental animals, Today, in a sense, the rest of medicine has caught up with nuclear medicine. Advances in molecular biology are based on the fact that all life is a chemical phenomenon, driven by an exquisite, exceedingly complex information processing system. Medical imaging processes information; nuclear medicine expresses that information in terms of regional chemistry. Every molecule in the body has a specific role and site of action. Every molecular can be labeled and "traced" using radioactive tracers for regions deep within the body and fluorescent tracers for regions close to the surface of the body, such as the eyes. skin or regions that can be seen via endoscopy.
Molecular biology has made gigantic strides in elucidating which molecules do what, beginning with the master molecule DNA. The Human Genome Program promises to complete a rough draft of the human genome by the spring of the year 2000, a year ahead of time. The rough draft will provide the sequences of 90% of tile human genome. But having all tile base pair sequences is only the start. What we need now is to find out the proteins that these genes produce and the functions of these proteins. One approach is to delete or "knock out" generate regions and observe structural or plasma biochemical effects. For example, deletion of parts of chromosome-11 in mice elevated triglyceride levels ten-fold in the circulating blood. Subsequent insertion of part of the human genome containing 120,000 bases corrected the high triglyceride levels and produced mice having normal life spans, induction of mutation by mutagenic chemicals is another approach to the search for phenotypic correlates of genes.
These approaches are examples of the "bottom-up" approach, where one starts with the gene {or parts of the gene}. The other approach is from the "top down", where one starts with a biochemical process in certain regions of the body, and carries out "gene hunts", that is, we try to deter- mine which genes are involved An example of fins approach is the story of multidrug resistance. Investigators in Toronto, Canada, found that patients with cancer who became resistant to the beneficial effects of chemotherapy were characterized by the presence of a protein, called p-glycoprotein, that brought about excretion of the chemotherapeutic agents from the cancel- cells, preventing their killing effect on the cancer cells, They then found that this protein was expressed by "multi-drug resistance (MDR) genes", that were present before treatment in some patients and developed during treatment in the patients who developed drug resistance. It was observed that tile radiotracer, technctium-99m sestimibi, used widely to examine regional myocardial blood flow in patients with coronary heart disease, was excreted from cancer cells that were resistant to chemotherapy. This information is useful in planning and monitoring chemotherapy. Thus, we see the circle beginning with phenotype (chemotherapy resistance) progressing to genotype (MDR genes), and then back to phenotype (tcchnctium-99m sestimibi imaging).
Another example of the synergism between nuclear