Imaging of cancer lipid metabolism in response to therapy

Lipids represent a diverse array of molecules essential to the cell's structure, defense, energy, and communication. Lipid metabolism can often become dysregulated during tumor development. During cancer therapy, targeted inhibition of cell proliferation can likewise cause widespread and drastic changes in lipid composition. Molecular imaging techniques have been developed to monitor altered lipid profiles as a biomarker for cancer diagnosis and treatment response. For decades, MRS has been the dominant non‐invasive technique for studying lipid metabolite levels. Recent insights into the oncogenic transformations driving changes in lipid metabolism have revealed new mechanisms and signaling molecules that can be exploited using optical imaging, mass spectrometry imaging, and positron emission tomography. These novel imaging modalities have provided researchers with a diverse toolbox to examine changes in lipids in response to a wide array of anticancer strategies including chemotherapy, radiation therapy, signal transduction inhibitors, gene therapy, immunotherapy, or a combination of these strategies. The understanding of lipid metabolism in response to cancer therapy continues to evolve as each therapeutic method emerges, and this review seeks to summarize the current field and areas of unmet needs. Lipids play critical roles in biological systems, ranging from structural integrity to trafficking, energy, defense, and communication. This article reviews lipids and lipid metabolic pathways altered in cancer development and their changes in response to therapy that are amenable for study by imaging. We focus first on MRS, which was instrumental in defining the field of lipid imaging (figure) and still plays a major role, followed by complementary molecular imaging methods including PET, mass spectroscopic imaging, and optical imaging.