Utilizing ¹⁸F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Abstract

A hallmark of advanced tumors is a switch to aerobic glycolysis that is readily measured by [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) imaging. Co-mutations in the KRAS proto-oncogene and the LKB1 tumor suppressor gene are frequent events in lung cancer that drive hypermetabolic, glycolytic tumor growth. A critical pathway regulating the growth and metabolism of these tumors is the mechanistic target of the rapamycin (mTOR) pathway, which can be effectively targeted using selective catalytic mTOR kinase inhibitors. The mTOR inhibitor MLN0128 suppresses glycolysis in mice bearing tumors with Kras and Lkb1 co-mutations, referred to as KL mice. The therapy response in KL mice is first measured by 18F-FDG PET and computed tomography (CT) imaging before and after the delivery of MLN0128. By utilizing 18F-FDG PET/CT, researchers are able to measure dynamic changes in the glucose metabolism in genetically engineered mouse models (GEMMs) of lung cancer following a therapeutic intervention with targeted therapies. This is followed by ex vivo autoradiography and a quantitative immunohistochemical (qIHC) analysis using morphometric software. The use of qIHC enables the detection and quantification of distinct changes in the biomarker profiles following treatment as well as the characterization of distinct tumor pathologies. The coupling of PET imaging to quantitative histology is an effective strategy to identify metabolic and therapeutic responses in vivo in mouse models of disease.

lncRNA GAS6-AS1 inhibits progression and glucose metabolism reprogramming in LUAD via repressing E2F1-mediated transcription of GLUT1

“…Lung cancer is the leading cause of cancer-related death, with limited curative treatment options, and extensive studies have revealed the reprogramming of glucose metabolism in lung cancer. 31 , 32 The alterations of oncogenes and tumor suppressor genes, leading to activation or inhibition of signaling pathways and transcriptional networks, were reported to participate in the glucose metabolism reprogramming of lung cancer. 33 However, the potential involvement of lncRNAs is poorly defined in glucose metabolism reprogramming of lung cancer.…”

Diagnostic Value of 18F-NOTA-FAPI PET/CT in a Rat Model of Radiation-Induced Lung Damage

“…To assess the specificity of 18 F-NOTA-FAPI accumulation and to confirm that uptake of 18 F-NOTA-FAPI in the area of RILD was due to saturable binding to FAP, a group of treated rats (n=3, day 42 after 90 Gy radiation treatment) were injected with 18 F-NOTA-FAPI and killed 1 h later. Serial short-axis cryosections 50-µm thick were prepared from the harvested lungs, and consecutive sections were used for autoradiography as previously described ( 20 , 21 ).…”

Long Noncoding RNA GAS6-AS1 Inhibits Progression and Glucose Metabolism Reprogramming in Lung Adenocarcinoma Via Repressing E2F1-Mediated Transcription of GLUT1

“…Lung cancer is the leading cause of cancer-related death with limited curative treatment options, and extensive studies have revealed the reprogramming of glucose metabolism in lung cancer [37,38]. The alterations of oncogenes and tumor suppressor genes, leading to activation or inhibition of signaling pathways and transcriptional networks, were reported to participate in the glucose metabolism reprogramming of lung cancer [39].…”