Molecular Imaging: Unveiling Metabolic Abnormalities in Pancreatic Cancer

Abstract

Pancreatic cancer remains one of the most aggressive malignancies globally, with a 5-year survival rate of less than 13%. This poor prognosis stems from late-stage diagnosis and intrinsic resistance to conventional therapies, including chemotherapy and radiotherapy. A hallmark of PC is oncogene-driven metabolic reprogramming-notably mediated by mutations in KRAS and other key pathways-which fuels tumor progression and undermines the efficacy of neoadjuvant treatments. Consequently, there is a pressing demand for non-invasive techniques capable of mapping metabolic alterations at both the tumor microenvironmental and systemic levels. This review will discuss molecular imaging techniques that identify metabolic changes within the tumor microenvironment. By bridging preclinical insights with clinical applications, we highlight how these innovations promise to revolutionize PC diagnosis, treatment stratification, and therapeutic monitoring, ultimately paving the way for precision oncology.

Keywords: metabolic imaging; molecular imaging; pancreatic cancer.

Figure 1

The landscape of key components in the metabolic imaging of PC. (Created in BioRender. Wang, A. (2025) https://BioRender.com/dekq39y). Key metabolites and targets for metabolic imaging and their metabolic processes are shown in the figure, with exogenous molecules highlighted in red boxes; 3-PG: 3-bisphosphoglycerate, ALT: alanine transaminase, CDA: cytidine deaminase, CoA: coenzyme A, CTL1: choline transporter like-protein 1, dCK: deoxycytidine kinase, DHAP: dihydroxyacetone phosphate, FAD: flavin adenine dinucleotide, fructose-6P: fructose 6-phosphate, fructose-1,6-biP: fructose 1,6-bisphosphate, R-NO2: NO2-containing molecular imaging probes, GA3P: glyceraldehyde 3-phosphate, GLUT1: glucose transporter 1, glucose-6P: glucose 6-phosphate, HK1/2: hexokinase 1/2, LDH: lactate dehydrogenase, MPC: mitochondrial pyruvate carrier, NAD: nicotinamide adenine dinucleotide, NADPH: nicotinamide adenine dinucleotide phosphate, OAA: oxaloacetate, TCA: tricarboxylic acid.

Figure 2

Probe structures or schematic diagrams of the probes for metabolic imaging. (Created in BioRender. Wang, A. (2025) https://BioRender.com/iihhl3v). (A) ¹⁸F-FDG; (B) [6,6-²H₂] glucose; (C) ¹³C-Glucose; (D) gemcitabine and ¹⁸F-FAC; (E) the metabolism of ¹³C-Pyruvate in cancer; (F) schematic diagrams of VEGFR2-targeted microbubbles.

Figure 3

Potential role of metabolic imaging in clinical decision-making. (Created in BioRender. Wang, A. (2025) https://BioRender.com/pcrjp4k).