Guest editorial: the conception of FDG-PET imaging.

T HE CONCEPT OF EMISSION and transmission tomography was introduced by David Kuhl and Roy Edwards in the late 1950s, which later led to the design and construction of several tomographic instruments at the University of Pennsylvania. These machines were able to successfully map regional distribution of radionuclides such a s 99mTc as tomographic images. The instruments built at the University of Pennsylvania were designed to detect single gamma emitters and therefore their research and clinical applications were limited to the investigation of simple functions like breakdowns in the blood-brain barrier in disorders such as brain tumors and cerebral infarcts. The instruments manufactured in the late 1960s and the early 1970s were also designed to image only the brain and not other organs, which was dictated by the technical difficulties that were encountered at the time. Collaboration between investigators from Nuclear Medicine and the Cerebrovascular Center at the University of Pennsylvania (directed by Martin Reivich) resulted in great interest in quantitative measurement of regional cerebral function such as blood flow and blood volume. Although these attempts were successfully implemented, it became clear that synthesizing biologically important compounds with single gamma-emitting radionuclides, like technetium and iodine, was a major challenge at the time and therefore other avenues were to be explored to overcome these limitations. By the early 1970s, Louis Sokoloff et al from the National Institutes of Health (NIH) and Martin Reivich from the University of Pennsylvania had clearly shown that the beta-emitting 14Cdeoxyglucose (DG) could be successfully used to map regional brain metabolism, which was later proven to correlate well with local function. These investigators were able to show that DG crosses the blood-brain barrier and is phosphorylated by the hexokinse system to DG-6-phosphate similarly to glucose. However, in contrast to glucose-6-phosphate, which is further metabolized to C O z and H20, DG-6-phosphate remains intact in the tissue for an extended period of time. This unique metabolic behavior makes radiolabeled deoxyglucose an excellent candidate for mapping regional function in the brain and other organs. Since ~4C is a beta-emitting radionuclide, optimal assessment of its distribution could be revealed by a technique called a u t o r a d i o g r a p h y . In animal experiments, 40 to 45 minutes after the intravenous administration of 14C-DG, slices of the brain were exposed to radiographic films to reveal the beta particles emitted for a period of time. The film was then processed to capture the regional distribution of the compound with exquisite detail. After successfully showing 14C-DG as a metabolic tracer, collaboration between investigators from the NIH and the University of Pennsylvania resulted in defining and measuring parameters that are essential for