Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-¹¹C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients’ survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.

Although extensive research on brown adipose tissue (BAT) has stimulated optimism in the battle against obesity and diabetes, BAT physiology and organ crosstalk are not fully understood. Besides BAT, melanin‐concentrating hormone (MCH) and its receptor (MCHR1) play an important role in energy homeostasis. Because of the link between hypothalamic MCH neurons and sympathetic BAT activation via β‐adrenoceptors, we investigated the expression and physiological role of the MCHR1 in BAT. MCHR1 was detected in rodent and human BAT with RT‐qPCR and western blot analyses. In vivo imaging in rats used the glucose analog [¹⁸F]FDG and the MCHR1‐tracer [¹¹C]SNAP‐7941. We found that the β3‐adrenoceptor (ADRB3) agonist CL316,243 increased [¹¹C]SNAP‐7941 uptake in BAT. Additionally, a pharmacological concentration of SNAP‐7941—a low‐affinity ADRB3 ligand—stimulated [¹⁸F]FDG uptake, reflecting BAT activation. In cultured human adipocytes, CL316,243 induced MCHR1 expression, further supporting a direct interaction between MCHR1 and ADRB3. These findings characterized MCHR1 expression in rodent and human BAT for the first time, including in vitro and in vivo data demonstrating a link between MCHR1 and the β3‐adrenergic system. The presence of MCHR1 in BAT emphasizes the role of BAT in energy homeostasis and may help uncover treatment approaches for obesity.

The glucose derivative 2-[¹⁸F]fluoro-2-deoxy-D-glucose (2-[¹⁸F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[¹⁸F]FDG is said to be trapped intracellularly as 2-[¹⁸F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[¹⁸F]FDG-6-phosphate and even postulating 2-[¹⁸F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[¹⁸F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[¹⁸F]FDG metabolism with intracellular tracer accumulation, efflux and the cells’ metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[¹⁸F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[¹⁸F]FDG-6-phosphate were 2-[¹⁸F]FDMannose-6-phosphate, 2-[¹⁸F]FDG-1,6-bisphosphate and 2-[¹⁸F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells’ metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[¹⁸F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[¹⁸F]FDG metabolism might help to improve cancer research and tumor diagnosis.

MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [ ¹¹ C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: p _{FWE+Bonferroni} < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transmen. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = −0.62, p _Bonferroni = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transmen. Highlights: Gender-affirming hormone therapy led to significant changes in gray matter density and microstructure in various brain regions Gray matter changes found after gender-affirming hormone therapy were not reflected by monoamone oxidase A density changes in the brain. Masculinizing gender-affirming hormone therapy resulted in increased sexual desire in transgender men.