Hyperpolarized C-13 studies of cancer metabolism in animal models. Hype or real?

Abstract

The Warburg effect [1–3] is the tendency of many cancer types to metabolize glucose into lactate via glycolysis rather than oxidation in the TCA cycle. While fermentative glycolysis is highly inefficient in terms of ATP production (indeed, it yields only about 1/9 of the ATP that would be produced by the TCA cycle), it may confer a survival advantage on cancer cells, for instance by providing a source of carbon to support rapid proliferation [4]. The Warburg effect, and cancer metabolism more generally, may provide opportunities for novel therapeutic strategies that target specific metabolic pathways that cancer cells rely upon for survival and proliferation. Recently, there have been reports that indicate that cancer cells can survive on glutamine as a carbon source, even when glucose is removed from their growth medium [5,6]. Imaging tools for the study of metabolism include PET and MR spectroscopic imaging. Metabolic studies with PET make use of metabolites that have been isotopically labeled with e emitters such as C or N, or, alternatively, where one or more protons have been substituted with F. Over the past several decades F-18 PET using fluoro-deoxyglucose as the radiotracer has been widely adopted in oncological imaging. There have other radiotracers that have shown promise for imaging different metabolic alterations in tumors [7]. The advantages of PET include its high sensitivity (some metabolites can be detected at picomolar concentrations) and the relatively long half-lives of the radiotracers (10 minutes for N, 20 minutes for C, and 110 minutes for F). The disadvantages of PET include limitations on spatial resolution imposed by positron ranging (the highest achievable resolution is on the order of a few millimeters) and the inability of PET to distinguish between signal arising from the injected radiotracer and its metabolites. For the shorter-lived isotopes like C-11, there is the need for both a cyclotron and chemistry facilities for rapid synthesis of desired radiolabeled compounds.