Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose

Abstract

Lung cancer has been the leading cause of cancer-related mortality in China in recent decades. Positron emission tomography-computer tomography (PET/CT) has been established in the diagnosis of lung cancer. 18F-FDG is the most widely used PET tracer in foci diagnosis, tumor staging, treatment planning, and prognosis assessment by monitoring abnormally exuberant glucose metabolism in tumors. However, with the increasing knowledge on tumor heterogeneity and biological characteristics in lung cancer, a variety of novel radiotracers beyond 18F-FDG for PET imaging have been developed. For example, PET tracers that target cellular proliferation, amino acid metabolism and transportation, tumor hypoxia, angiogenesis, pulmonary NETs and other targets, such as tyrosine kinases and cancer-associated fibroblasts, have been reported, evaluated in animal models or under clinical investigations in recent years and play increasing roles in lung cancer diagnosis. Thus, we perform a comprehensive literature review of the radiopharmaceuticals and recent progress in PET tracers for the study of lung cancer biological characteristics beyond glucose metabolism.

3’-O-β-Glycosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase

“…15,16 In humans, hENT1 is the main protein responsible for the transport of nucleosides, including many pharmaceutically relevant analogues such as gemcitabine and for which resistance profiles have rapidly developed. 17 This phenotypic change towards increased glucose uptake as a result of upregulated GLUT expression, has led to the widespread clinical use of 18 fluorodeoxyglucose positron-emission tomography (FDG-PET) as a method of detecting and staging various cancers. 18,19 Glufosfamide 20 and an aroylhydrazone glycoconjugate prochelator 21 have both been demonstrated to rely on uptake by GLUT1 to facilitate cytotoxic activity.…”

“…17 This phenotypic change towards increased glucose uptake as a result of upregulated GLUT expression, has led to the widespread clinical use of 18 fluorodeoxyglucose positron-emission tomography (FDG-PET) as a method of detecting and staging various cancers. 18,19 Glufosfamide 20 and an aroylhydrazone glycoconjugate prochelator 21 have both been demonstrated to rely on uptake by GLUT1 to facilitate cytotoxic activity.…”

Synthesis, radiolabeling, and evaluation of 68Ga-labeled aminoquinoxaline derivative as a potent PFKFB3-targeted PET tracer

“…With the goal to develop novel PFKFB3 PET tracers for tumor diagnosis, we performed the structural modification to the aminoquinoxaline scaffold and radiolabeled with 68 Ga for in vitro and in vivo evaluations. With a similar structure of glucose, 18 F-fluorodeoxyglucose ( 18 F-FDG) is able to visualize the abnormal glucose metabolism and hence has been widely used for the diagnosis of tumors ( Jadvar et al, 2009 ; Zhu et al, 2022 ). However, the accumulation of 18 F-FDG mainly revels the activity of glucose transporters (GLUT) in tumor cells and tissues, the biomarker for tumor glycolysis may play more important role in tumor diagnosis, such as PFKFB3 ( Ganapathy-Kanniappan and Geschwind, 2013 ; Meziou et al, 2020 ).…”