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This review aims to emphasize the potential of in vivo imaging to optimize current and upcoming anti-cancer immunotherapies: spanning from preclinical to clinical applications. Immunotherapies are an emerging class of treatments for a variety of diseases. The agents include molecular and cellular therapeutics, which aim to treat the disease through re-education of the host immune system, often via complex mechanisms of action. In vivo imaging has the potential to contribute in several different ways: (1) as a drug development tool to improve our understanding of their complex mechanisms of action, (2) as a tool to predict efficacy, for example, to stratify patients into probable responders and likely non-responders, and (3) as a non-invasive treatment response biomarker to guide efficient immunotherapy use and to recognize early signs of potential loss of efficacy or resistance in patients. Areas where in vivo imaging is already successfully implemented in onco-immunology research will be discussed and domains where its use offers great potential will be highlighted. The focus of this article is on anti-cancer immunotherapy as it currently is the most advanced immunotherapy area. However, the described concepts can also be paralleled in other immune-mediated disorders and for conditions requiring immunotherapeutic intervention. Importantly, we introduce a new study group within the European Society of Molecular Imaging with the goal to facilitate and enhance immunotherapy development through the use of in vivo imaging. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-13C-pyruvate magnetic resonance spectroscopy (MRS) and 19F magnetic resonance imaging (MRI), respectively.Procedure: Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-13C-pyruvate into hyperpolarized 1-13C-lactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles.Results: Hyperpolarized 1-13C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum transfer, which remained elevated during the progression of the disease, while 19F-MRI exhibited a gradual recruitment of phagocytic immune cells in arthritic ankles, which correlated well with the course of ankle swelling. Histopathology and IHC revealed that MCT-1 was expressed in regions with inflammatory cell recruitment, confirming the metabolic shift identified in arthritic ankles.Conclusions: Our study demonstrated the presence of a very early metabolic shift in arthritic joints independent of phagocytic immune cell recruitment. Thus, hyperpolarized 1-13C-pyruvate represents a promising tracer to monitor acute arthritic joint inflammation, even with minor ankle swelling. Furthermore, translated to the clinics, these methods add a detailed characterization of disease status and could substantially support patient stratification and therapy monitoring. [ABSTRACT FROM AUTHOR]