Monoclonal gammopathy-associated atypical hemolytic uremic syndrome: A relevant concept?

Abstract

Cancer and other diseases are increasingly understood in terms of their metabolic disturbances. This thinking has revolutionized the field of ex vivo metabolomics and motivated new approaches to detect metabolites in living systems, including proton magnetic resonance spectroscopy (1H-MRS), hyperpolarized 13C MRS, and PET. For PET, imaging abnormal metabolism in vivo is hardly new. Positron-labeled small-molecule metabolites have been used for decades in humans, including 18F-FDG, which is used frequently to detect upregulated glycolysis in tumors. Many current 18F metabolic tracers including 18F-FDG have evolved from their 11C counterparts, chemically identical to endogenous substrates and thus approximating intrinsic biochemical pathways. This mimicry has stimulated the development of new radiochemical methods to incorporate 11C and inspired the synthesis of a large number of 11C endogenous radiotracers. This is in spite of the 20-minute half-life of 11C, which generally limits its use in patients to centers with an on-site cyclotron. Innovation in 11C chemistry has persisted in the face of this limitation, because (1) the radiochemists involved are inspired, (2) the methods of 11C incorporation are diverse, and (3) 11C compounds often show more predictable in vivo behavior, thus representing an important first step in the validation of new tracer concepts. In this mini-review we will discuss some of the general motivations behind PET tracers, rationales for the use of 11C, and some of the special challenges encountered in the synthesis of 11C endogenous compounds. Most importantly, we will try to highlight the exceptional creativity used in early 11C tracer syntheses, which used enzyme-catalyzed and other “green” methods before these concepts were commonplace.