Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

Background: A growing body of evidence highlights sex differences in the diagnostic accuracy of cardiovascular imaging modalities. Nonetheless, the role of sex hormones in modulating myocardial perfusion and coronary flow reserve (CFR) is currently unclear. The aim of our study was to assess the impact of female and male sex hormones on myocardial perfusion and CFR. Methods: Rest and stress myocardial perfusion imaging (MPI) was conducted by small animal positron emission tomography (PET) with [¹⁸F]flurpiridaz in a total of 56 mice (7–8 months old) including gonadectomized (Gx) and sham-operated males and females, respectively. Myocardial [¹⁸F]flurpiridaz uptake (% injected dose per mL, % ID/mL) was used as a surrogate for myocardial perfusion at rest and following intravenous regadenoson injection, as previously reported. Apparent coronary flow reserve (CFR_App) was calculated as the ratio of stress and rest myocardial perfusion. Left ventricular (LV) morphology and function were assessed by cardiac magnetic resonance (CMR) imaging. Results: Orchiectomy resulted in a significant decrease of resting myocardial perfusion (Gx vs. sham, 19.4 ± 1.0 vs. 22.2 ± 0.7 % ID/mL, p = 0.034), while myocardial perfusion at stress remained unchanged (Gx vs. sham, 27.5 ± 1.2 vs. 27.3 ± 1.2 % ID/mL, p = 0.896). Accordingly, CFR_App was substantially higher in orchiectomized males (Gx vs. sham, 1.43 ± 0.04 vs. 1.23 ± 0.05, p = 0.004), and low serum testosterone levels were linked to a blunted resting myocardial perfusion (r = 0.438, p = 0.020) as well as an enhanced CFR_App (r = −0.500, p = 0.007). In contrast, oophorectomy did not affect myocardial perfusion in females. Of note, orchiectomized males showed a reduced LV mass, stroke volume, and left ventricular ejection fraction (LVEF) on CMR, while no such effects were observed in oophorectomized females. Conclusion: Our experimental data in mice indicate that sex differences in myocardial perfusion are primarily driven by testosterone. Given the diagnostic importance of PET-MPI in clinical routine, further studies are warranted to determine whether testosterone levels affect the interpretation of myocardial perfusion findings in patients.

ATP synthase dysregulation has been implicated in many diseases, including cancer and neurodegenerative diseases. Whilst ATP synthase‐targeting compounds have been reported, most are large or polar compounds and lack appropriate properties for a CNS drug. We designed, synthesised, and evaluated a novel series of ATP synthase targeting compounds, resulting in a 1,3,4‐oxadiazin‐5‐one scaffold with improved physiochemical properties. In vitro evaluation of our library led to the discovery of CJ1‐34 as a partial ATP synthase inhibitor with a determined IC ₅₀ of 394 nM in isolated bovine mitochondria. Molecular docking experiments demonstrated that calculated docking scores aligned with the observed in vitro pharmacology and supports the F ₁ region of the ATP synthase as the potential binding site. Overall, this provides the foundation to further investigate CJ1‐34 as a potential CNS drug for diseases where mitochondria are implicated, including Alzheimer's and Parkinson's disease.

Adipose tissue has gained increasing attention as a therapeutic target to combat human obesity and related metabolic disorders. We propose ATP synthase as a target to identify activated and non-activated adipose tissue. We investigated ATP synthase using the radiotracer [ ¹¹ C]J147 and confirmed the specificity of the radiotracer by in vitro autoradiography, cell knockdown studies, and in vivo competition binding studies. In addition to the interscapular brown adipose tissue (BAT), [ ¹¹ C]J147 could visualise several other BAT depots (supraspinal, infrascapular and axillary BAT) via in vivo positron emission tomography imaging after activation with a β ₃ -adrenergic receptor agonist, as confirmed by immunohistochemistry and biodistribution studies. Furthermore, [ ¹¹ C]J147 demonstrated higher sensitivity for BAT and WAT (white adipose tissue) identification compared to the commonly used radiotracer [ ¹⁸ F]FDG and the mitochondrial complex I tracer [ ¹⁸ F]BCPP-EF. Our study uncovers ATP synthase as a promising target for monitoring adipose tissue and [ ¹¹ C]J147 could facilitate drug development for metabolic diseases such as obesity.