European Journal of Nuclear Medicine and Molecular Imaging | 2019
An update on the unparalleled impact of FDG-PET imaging on the day-to-day practice of medicine with emphasis on management of infectious/inflammatory disorders
Abstract
The concept of FDG-PET imaging was discussed for the first time among three investigators from the University of Pennsylvania, Abass Alavi, David Kuhl, and Martin Reivich, in the early 1970s [1]. These investigators had realized the potential for this novel radiolabeled compound in human research and clinical practice based on autoradiographic imaging studies using 14C-deoxyglucose in animals [1]. This initial discussion led to contacting chemists at the Brookhaven National Laboratory (BNL), which soon led to a joint effort to label deoxyglucose with 18F and determine its role by examining brain function in human beings. This investigation was led by AlfredWolf and his colleagues at BNL and eventually, the compound was successfully synthesized and tested for toxicity before plans were made to image its distribution in human beings [2]. By mid-1976, an investigational new drug (IND) application was secured from the FDA for administering this radiotracer to normal human volunteers. Finally, in August 1976, the compound was shipped by a private plane to Philadelphia and successful images of the whole body by a conventional rectilinear scanner and tomographic images by a SPECT instrument were acquired by Abass Alavi at the University of Pennsylvania [3]. Soon thereafter, research protocols were drafted to determine the patterns of cerebral glucose metabolism with this compound in central nervous system disorders by Penn/BNL and UCLA investigators [4, 5]. The results from these early research studies conducted initially at these institutions and then later by a few other centers in the USA and Europe in the 1980s clearly demonstrated the great promise of FDG for both research and clinical applications. In spite of the complexity and technical challenges that were faced by this demanding technology, over the past 4 decades, the role of this powerful imaging modality has been validated and well-established for assessing numerous disorders [6, 7]. Soon after its introduction, this approach was proven to be of great value in diagnosing Alzheimer’s disease with very high sensitivity and specificity which has remained unmatched by any other technique to date [8–10]. Other applications in the 1980s and 1990s included detection of seizure focus in temporal lobe epilepsy [11–13], vascular disorders [14], and a variety of neuropsychiatric diseases such as schizophrenia and manic depression [15–18]. However, the major observation that was made from the early research studies in animal [19] and in human brain images with FDG was its critical role in detecting and characterizing malignant cells, particularly, brain tumors [20, 21]. These early research projects were carried out by investigators at BNL, Penn, and NIH. For the first time, the observation that was described by Warburg in the in vitro setting, where he was able to demonstrate high glycolytic activity of cancer cells compared with normal tissues, was verified by in vivo imaging with FDG [22, 23]. The latter further enhanced the potential for employing FDG-PET imaging to expand the horizons of this powerful methodology beyond central nervous system disorders. In parallel with synthesis of FDG and testing its novel application in human diseases and disorders, efforts by Michael TerPogossian and colleagues at Washington University had resulted in designing and testing early PET This article is part of the Topical Collection on Editorial