Anne Roivainen

Prostate cancer was the most frequently diagnosed cancer and the second leading cause of cancer-related death among men in the United States in 2025. Prostate-specific membrane antigen (PSMA)-targeted PET tracers have significantly improved the detection, visualization, and staging of prostate cancer. Recently, the novel prosthetic group [18F]AmBF3-Tz was introduced, combining simple isotopic 18F-radiolabeling of alkylammoniomethyltrifluoroborates (AmBF3) with efficient bioorthogonal tetrazine-trans-cyclooctene (TCO) conjugation. This study evaluated the suitability of [18F]AmBF3-Tz for radiolabeling PSMA-targeting urea derivatives and assessed its impact on PSMA-binding affinity in vitro and in vivo. Four precursors─TCO-PSMA, TCO-tranexamic acid-PSMA, AmBF3-PSMA, and AmBF3-tranexamic acid-PSMA─were synthesized and used for the preparation of [18F]AmBF3-PSMA and [18F]AmBF3-tranexamic acid-PSMA via one-step or two-step labeling strategies. Conjugation before radiolabeling gave radiochemical yields of 5.2–11.8%, whereas the two-step method gave 0.7–9.8%. Although these yields demonstrate feasibility, they are lower and more variable than the 33 ± 5% yield obtained for [18F]AmBF3-Tz and would require substantial optimization before clinical translation. Overall, [18F]AmBF3-PSMA and [18F]AmBF3-tranexamic acid-PSMA demonstrated PSMA-specific tumor uptake and enabled the visualization of C4-2 xenografts. The tranexamic acid-containing tracer showed higher tumor-to-background ratios than [18F]AmBF3-PSMA in this study, but the absolute tumor uptake was not significantly different between the two tracers. The moderate and variable radiochemical yields, microscale reaction sensitivity, and small animal group sizes indicate that this proof-of-concept platform warrants further optimization before its suitability for clinical translation can be assessed.

Aims: Obesity, marked by excess adipose tissue, is strongly associated with increased cardiometabolic risk. Metabolic bariatric surgery (MBS) leads to significant and sustained weight loss and improves metabolic profiles in persons with severe obesity. However, how MBS induces persistent transcriptional changes in adipose tissue and their contributions to cardiometabolic improvements remain unclear. This study examined subcutaneous (SAT) and visceral (VAT) adipose tissue transcriptome profiles in people with severe obesity, tracking changes in SAT after MBS, with a focus on lipid metabolism, inflammation, RNA processing, and cholesterol handling. Methods: This study included 42 women with severe obesity undergoing MBS and 15 sex-matched healthy people without obesity as controls. Targeted RNA expression profiling was performed on SAT and VAT samples. Results: In people with obesity, SAT showed higher expression of genes related to adipocyte function, anti-inflammatory markers, extracellular matrix remodeling, lipid metabolism, cell-death regulation, oxidative stress protection, mRNA processing, and cholesterol handling compared to VAT. In contrast, VAT showed elevated expression of genes linked to inflammation, complement activation, stress signaling, cell death, lipid biosynthesis, and mRNA processing. Compared with controls, SAT in obesity showed increased inflammatory and stress-response gene expression and upregulation of RNA processing regulators, but reduced de novo lipogenesis and cholesterol synthesis. Following MBS, SAT showed restored expression of lipogenic and adipogenic genes alongside downregulation of inflammatory, cholesterol biosynthesis, and splicing-factor genes. Conclusions: These findings demonstrate SAT and VAT remodeling in obesity and show that MBS partially reverses transcriptional changes in SAT, providing mechanistic insight into its metabolic benefits. They also highlight the need for targeted therapeutic strategies to more fully restore adipose tissue function and improve long-term metabolic outcomes. ClinicalTrials.gov registration numbers: NCT00793143 and NCT01373892.

Introduction: We evaluated the trajectories of echocardiographic myocardial work (MW) indices and their associations with left ventricle (LV) functional recovery, myocardial viability, and perfusion in patients with reperfused acute myocardial infarction (AMI). Methods: Thirty-one patients with a first ST-elevation AMI treated with percutaneous coronary intervention were prospectively enrolled. Transthoracic echocardiography and [ ¹⁵ O]-water positron emission tomography (PET) were performed at a median of 7.7 ± 3.8 days post- intervention (baseline). Global and segmental absolute myocardial blood flow (MBF) were assessed using PET, and myocardial segments were graded as viable or non-viable based on perfusable tissue fraction (PTF). Echocardiographic parameters, including LV ejection fraction (LVEF), global longitudinal strain (GLS), myocardial work index (MWI), constructive work (MCW), wasted work (MWW), and work efficiency (MWE), were measured at baseline and at the 6-month follow-up. The myocardial area at risk (AAR) and the remote myocardium were defined based on the culprit coronary artery segment. Results: LVEF and GLS remained unchanged between baseline and follow-up. However, global MWI, MCW, and MWE significantly increased, while MWW decreased at the 6 months (all p < 0.05). An increase in MWI, but not MWE, was associated with improvement of LVEF. Neither global MWI nor MWE correlated with global MBF, but were inversely associated with peak levels of troponin T and NT-proBNP. In the AAR, regional MWI and MWE were significantly correlated with regional MBF ( r = 0.53, p = 0.003, and r = 0.59, p < 0.001, respectively) and PTF ( r = 0.41, p = 0.03, and r = 0.65, p < 0.001, respectively). At baseline, segmental MWI and MWE were higher in viable compared to non-viable segments. At 6 months, MWI and MWE increased in viable, but not in non-viable segments. Conclusions: Echocardiographic myocardial work indices reflect the severity of myocardial injury early after AMI and may serve as non-invasive markers of functional recovery and myocardial viability.

Rationale: The μ-opioid receptor (MOR) is widely expressed across tissues and plays crucial roles in pain and stress responses, social behaviour, and immune regulation. Recent evidence indicates seasonal variation in in vivo MOR signalling; for example, short photoperiods are associated with reduced central MOR availability, increased MOR expression in brown adipose tissue (BAT), and strengthened brain–BAT interactions. However, despite this coupling with photoperiod, it remains unclear whether static daylength and dynamically changing photoperiods exert distinct effects, as adaptation to photoperiod transitions may itself induce stress-related modulation of the MOR system. Elucidating how seasonal, stress-related adaptations influence MOR signalling is essential for advancing our understanding of seasonal fluctuations in mood and stress regulation. Methods: We compared rats housed under seasonal photoperiod cycling with those maintained under constant photoperiod conditions, using ex vivo radioligand binding to directly assess MOR density in central and peripheral tissues. Results: Rats exposed to seasonal photoperiod cycling showed markedly reduced inter-individual variability in MOR density in both the brain (including the cerebellum and striatum) and peripheral tissues (adrenal glands), whereas no tissues exhibited substantially increased variability. Conclusions: These findings demonstrate that seasonal photoperiod cycling stabilizes MOR dynamics at the population level, suggesting stress-related synchronization of MOR signalling. The findings deepen our understanding of seasonal effects on endogenous MOR signalling, and further underscore the role of seasonal light variation in modulating mood-related processes.

L-Lactate is a key substrate in energy metabolism and a potential biomarker for cancer and metabolic disorders. We developed an enantiomerically pure positron emission tomography (PET) tracer, (R)-[18F]fluorolactate, to mimic natural L-lactate. (R)-[18F]Fluorolactate was synthesized via nucleophilic ring-opening of benzyl (S)-oxirane-2-carboxylate, optimized to yield >91% radiochemical purity, > 95% enantiomeric excess, pH 6, and >5.56 GBq/μmol molar activity. PET/computed tomography (CT) imaging, biodistribution, autoradiography, and stability analyses were conducted in fasted and nonfasted rats and in mice bearing subcutaneous Lewis lung carcinoma (LLC) tumors. In rats, tracer uptake was highest in the kidneys and liver, with fasting further increasing renal and hepatic uptake. In mice, (R)-[18F]fluorolactate accumulated in tumors. The monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 significantly reduced tracer uptake in normal tissues and LLC tumors, and increased renal excretion, confirming MCT1-mediated transport. More than 80% and 90% of the tracer remained intact in plasma at 70 min postinjection in rats and tumor-bearing mice, respectively. In silico structural analyses supported the experimental findings. (R)-[18F]Fluorolactate is a metabolically stable, MCT1-sensitive PET tracer suitable for noninvasive assessment of lactate transport and metabolism and shows promise for imaging MCT1-dependent lactate transport in cancer.