Potential Value of Positron Emission Tomography (PET) in Evaluating the Ketogenic Diet as Anticancer Therapy

Positron Emission Tomography(PET) imaging is a noninvasive and extraordinarily sensitive imaging modality that provides a functional and metabolic assessment of normal or diseased tissue. [18F]-fluorodeoxyglucose PET imaging(FDG PET) is widely used clinically for tumor imaging, and has been proven to improve the diagnosis and subsequent treatment of cancer patients. The rationale behind FDG PET imaging is the Warburg effect, which states that there is increased glycolysis in cancer cells, even in the presence of oxygen, making it possible to detect cells exhibiting increased glycolysis, thus diagnosing even small tumors. The ketogenic diet(KD) with low carbohydrate and high fat intake has been used as an alternative treatment for cancer and other diseases, with nearly a century of use for reducing seizure onset in epileptics. The cellular mechanism underlying KD therapy is also based on the Warburg effect. The increased ketolysis stimulated by KD therapy inhibits the abnormally elevated glycolysis in cancer cells, leading to reduced tumor growth and metastasis. In this review, we first describe the Warburg effect as the common biological basis connecting PET and KD therapy. This paper also provides overviews of PET imaging and KD therapy. Two newly published papers, one regarding the molecular mechanism of KD therapy in the treatment of cancers, another on the in vivo PET imaging of cerebral metabolism of glucose and ketone bodes in humans after a moderate KD, are thoroughly reviewed. Furthermore, this review describes how PET imaging may be applied to study the effects of KD therapy in humans and animals, and which currently available PET tracers can be used to image glucose and ketone metabolic pathways.