Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective

Arginase is a widely known Enzyme of the urea cycle that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. The action of Arginase goes beyond the boundaries of hepatic ureogenic function, being widespread through most tissues. Two Arginase isoforms coexist, the type I (Arg1) predominantly expressed in the liver and the type II (Arg2) expressed throughout extrahepatic tissues. By producing L-ornithine while competing with nitric oxide synthase (NOS) for the same substrate (L-arginine), Arginase can influence the endogenous levels of polyamines, proline, and NO^•. Several pathophysiological processes may deregulate Arginase/NOS balance, disturbing the homeostasis and functionality of the organism. Upregulated Arginase expression is associated with several pathological processes that can range from cardiovascular, immune-mediated, and tumorigenic conditions to neurodegenerative disorders. Thus, Arginase is a potential biomarker of disease progression and severity and has recently been the subject of research studies regarding the therapeutic efficacy of Arginase inhibitors. This review gives a comprehensive overview of the pathophysiological role of Arginase and the current state of development of Arginase inhibitors, discussing the potential of Arginase as a molecular imaging biomarker and stimulating the development of novel specific and high-affinity Arginase imaging probes.

arginase; arginase inhibitors; molecular imaging; nitric oxide; positron emission tomography (PET).