Nuclear Imaging of Glucose Metabolism: Beyond ¹⁸F-FDG

Abstract

Glucose homeostasis plays a key role in numerous fundamental aspects of life, and its dysregulation is associated with many important diseases such as cancer. The atypical glucose metabolic phenomenon, known as the Warburg effect, has been recognized as a hallmark of cancer and serves as a promising target for tumor specific imaging. At present, 2-deoxy-2-[18F]fluoro-glucose (18F-FDG)-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for this purpose. The powerful impact of 18F-FDG has prompted intensive research efforts into other glucose-based radiopharmaceuticals for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. Currently, glucose and its analogues have been labeled with various radionuclides such as 99mTc, 111In, 18F, 68Ga, and 64Cu and have been successfully investigated for tumor metabolic imaging in many preclinical studies. Moreover, 99mTc-ECDG has advanced into its early clinical trials and brings a new era of tumor imaging beyond 18F-FDG. In this review, preclinical and early clinical development of glucose-based radiopharmaceuticals for tumor metabolic imaging will be summarized.

From Glucose to Lactate and Transiting Intermediates Through Mitochondria, Bypassing Pyruvate Kinase: Considerations for Cells Exhibiting Dimeric PKM2 or Otherwise Inhibited Kinase Activity

“…It is a well-known fact that most cancers exhibit increased rates in glucose consumption (Bose and Le, 2018). This is clinically exploited by following radionuclide-labeled glucose analogs for the purpose of tumor imaging in living human beings (Feng et al, 2019). The very same cancers are also known to be major lactate producers, which is important for their survival (de la Cruz-Lopez et al, 2019).…”

Towards the Development of a Targeted Albumin-Binding Radioligand for Theranostic Applications: Synthesis, Radiolabelling and Preliminary In Vivo Studies

“…[18,19] The most widely used radiopharmaceutical that exploits this property for cancer diagnosis is [ 18 F]Fluorodeoxyglucose ([ 18 F]FDG) [20] and based on this same principle of GLUT and glycolysis targeting, a few other glucose analogue targeting agents have also been developed. [21][22][23][24] Most recently, a glucose-targeted probe (1380 g/mol) for photoacoustic and fluorescent imaging was proven to have cell uptake through GLUT. [25] The tetra-amine macrocycle, cyclam, was identified as the chelating agent, as it is cheap and readily available and has been widely used in a number of compounds for medicinal applications, including PET imaging and for the complexation of a number of different metals with very good in vivo stability.…”

Next-Generation Molecular Imaging of Thyroid Cancer

“…Thus, in these entities, [ 18 F]FDG PET/CT imaging is useful in initial diagnosis, subsequent disease grading, treatment, and follow-up after treatment. Even though numerous glucose analog tracers other than [ 18 F]FDG were created [56], their head-to-head comparisons with the widely used [ 18 F]FDG are lacking.…”