Comparison of tumor uptake of the radiotracers targeting cancer metabolism

The distinct metabolism of cancer cells relying on glycolysis is gaining renewed attention as a “hallmark of cancer” (1) since its close connection to alteration in oncogenes and signaling pathways has been revealed. Why cancer cells rely on glycolysis, an inefficient process to produce ATP, is not fully understood, however, a probable cause proposed is that the products of glycolysis can be used to meet the need for large amount of substrate to support the rapid proliferation (2). The importance of glutamine metabolism, in addition to glucose, has been reported recently. Various pharmaceuticals targeting the cancer metabolism have been developed both for therapy and diagnosis. As PET radiopharmaceuticals, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) for glucose metabolism is widely used in clinics, along with 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT) reflecting DNA synthesis and [11C]acetate for fatty acid synthesis. The development of PET radiopharmaceuticals for glutamine metabolism is also quite active. The tumor accumulation of these pharmaceuticals are expected to predict prognosis, although there still is some controversy and the relation of their accumulation to each other needs more examination.In this study, to examine the above relation, we compared tumor accumulation and intratumoral distribution of FDG, FLT, acetate and glutamine, administering two radiotracers with different half-lives in combination, [18F]FLT and [14C]FDG for example, into tumor bearing mice. In the double tracer biodistribution study, positive correlation was only observed between FDG and glutamine, and FLT and acetate. The intratumoral distributions of the two tracers in the above two combinations showed similarity, but in the other combinations the two tracers often showed different pattern. From our observation, accumulation and intratumoral distribution of the four PET pharmaceuticals or tracers, FDG, FLT, acetate and glutamine, could be different, although they are all supposed to reflect tumor cell proliferation. Some caution may be necessary when we are interpreting their tumor accumulation.2015 World Molecular Imaging Congress (WMIC