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Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics. At present, various imaging agents have been prepared and evaluated in MM at preclinical and clinical levels. A summary overview of molecular functional imaging in MM is provided, and commonly used radiotracers are characterized.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

Selective modulation of metabotropic glutamate receptor 2 (mGlu2) represents a novel therapeutic approach for treating brain disorders, including schizophrenia, depression, Parkinson’s disease (PD), Alzheimer’s disease (AD), drug abuse and addiction. Imaging mGlu2 using positron emission tomography (PET) would allow in vivo quantification under physiological and pathological conditions and facilitate drug discovery by enabling target engagement studies. However, to date, few successful efforts have been disclosed to visualize mGlu2 in vivo, indicating an unmet and urgent clinical need. Herein we report the synthesis and preclinical evaluation of a focused library of mGlu2 modulators amenable for radiolabeling. The promising candidate 4-(2,4-difluorophenyl)-7-((2-methoxypyridin -4-yl)methyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-2-carboxamide (21b), exhibited high potency and excellent subtype selectivity, which was then evaluated by in vitro autoradiography and in vivo PET imaging studies after labeling with carbon-11. Ligand [11C]21b (also known as [11C]MG2-1904) demonstrated high brain uptake and excellent in vitro/in vivo specific binding towards mGlu2 with high metabolic stability in the brain. As proof-of-concept, our preliminary work demonstrated a successful example of visualizing mGlu2 in vivo derived from negative allosteric modulators (NAMs), which represents a promising chemotype for further development and optimization aimed for clinical translation.

To better apply microwave technology to surimi industry, surimi gels of different thicknesses were investigated. According to the determination of electromagnetic properties of surimi paste, both the maximum penetration depth and absorption peak are less than 1 cm. The results of temperature distribution shown that the highest temperature point of the surimi shifted from the center to the periphery. The coefficient of variation (COV) was the minimum and the temperature distribution the temperature distribution was the most uniform when the surimi thickness was 2.0 cm. Surimi paste with a thickness of 2.0 cm heated by microwaves (2450 MHz) had higher gel properties (16.42 ± 0.22 MPa) and water holding capacity (73.59 ± 0.26%) compared to that heated by the traditional water bath method. Scanning electron microscopy revealed that an ordered and dense network structure formed at a thickness of 2 cm. The optimum thickness (2 cm) for microwave heating was determined based on the electromagnetic characteristics and the temperature distribution of surimi, which provided basis for the application of microwave in surimi products.

Objectives: The translocator protein 18 kDa (TSPO), whose expression is upregulated by the activation of glia cells, is a continuously attractive biomarker for exploring neuroinflammation and neurologic disorders such as AD, PD and multiple sclerosis by PET. However, most TSPO PET tracers are sensitive to rs6971 polymorphism in human. In this study, we aim to identify some potential 18F-labeled PET tracers with high affinities, good brain uptake as well as reasonable insensitivity to rs6971 polymorphism. Methods: Through the structure-activity relationship study, two novel candidates with aryl fluorine moiety, namely LW-1-F and LW-2-F, were screened with high TSPO binding affinities. The corresponding 18F-isotopologues, 18F-LW-1 and 18F-LW-2, were synthesized automatically via spirocyclic iodonium ylide (SCIDY) strategy by CFN-MPS200 module. Dynamic neuroPET imaging were performed on wild-type Sprague-Dawley (SD) rats. The specificities and sensitivities to rs6971 polymorphism were evaluated by autoradiography (ARG) with LAB and HAB postmortem human brain slices. The pharmacokinetics were explored on mice by ex vivo biodistribution (bioD). Results: Both LW-1-F and LW-2-F showed excellent binding affinity with Ki < 0.1 nM. For radiofluorination, the corresponding SCIDY precursors were successfully obtained as colorless solids. The radiochemical yields were 16 ± 5% (n.d.c, n = 4, 18F-LW-1) and 15 ± 7% (n.d.c., n = 4, 18F-LW-2), respectively. The total radiosynthesis time was less than 90 min with good molar activities (> 1 Ci/μmol) and radiochemical purities (> 99%). MicroPET imaging showed that 18F-LW-1 penetrated the blood-brain-barrier (BBB) of SD rat, with the highest whole brain uptake as 1.38 SUV at 2 min post-injection, and gradually washed out to 0.7 SUV after 20 min and remained at this level. The ARG results from human brain slices showed a certain level of sensitivity to rs6971 (ratioHAB/LAB = 1.7) and nonspecific binding. 18F-LW-2 showed reasonable insensitivity (ratioHAB/LAB = 1.1) and excellent in vitro specific binding by ARG study. Ex vivo biodistribution of 18F-LW-2 showed high radioactivity accumulation in the lungs, heart, kidney and adrenal glands, as well as urinary and hepatobiliary excretion. Conclusions: We have efficiently synthesized a series of novel TSPO ligands with aryl fluorine skeleton. Specifically, LW-1-F and LW-2-F showed good binding affinity to TSPO, which were successfully radiolabeled for imaging study. The microPET, in vitro ARG and ex vivo bioD study revealed that 18F-LW-2 showed good specificity, pharmacokinetics as well as reasonable insensitivity to rs6971 polymorphism, which is a potential PET tracer for visualizing TSPO in human., SNMMI 2020 Annual Meeting