Introduction: Brain distribution of synaptic vesicle protein 2A was measured with fluorine‐18 UCB‐H ([ ¹⁸ F]UCB‐H) and positron emission tomography (PET). Methods: Images of synaptic density were acquired in healthy volunteers (two young participants and two seniors). Input function was measured by arterial blood sampling (arterial input function) and derived from PET images using carotid activity (image‐derived input function). Logan graphical analysis was used to estimate regional synaptic vesicle protein 2A distribution volume. Results: [ ¹⁸ F]UCB‐H uptake was ubiquitous in cortical and subcortical gray matter. Arterial input function and image‐derived input function provided regional distribution volume with a high linear relationship. Discussion: The cerebral distribution of [ ¹⁸ F]UCB‐H is similar to that recently observed with carbon‐11 UCB‐J ([ ¹¹ C]UCB‐J). An accurate [ ¹⁸ F]UCB‐H quantification can be performed without invasive arterial blood sampling when no suitable reference region is available, using dynamic PET carotid activity. Brain synaptic density can be studied in vivo in normal and pathological aging.

Serotonin 1A (5-HT_1A) receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target. The recent pharmacological concept of biased agonism asserts that highly selective agonists can preferentially direct receptor signaling to specific intracellular responses, opening the possibility of drugs targeting a receptor subtype in specific brain regions. The present study brings additional support to this concept thanks to functional magnetic resonance imaging (7 Tesla-fMRI) in anaesthetized rats. Three 5-HT_1A receptor agonists (8-OH-DPAT, F13714 and F15599) and one 5-HT_1A receptor antagonist (MPPF) were compared in terms of influence on the brain blood oxygen level-dependent (BOLD) signal. Our study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist. By providing functional information on the influence of pharmacological activation of 5-HT_1A receptors in specific brain regions, this neuroimaging approach, translatable to the clinic, promises to be useful in exploring the new concept of biased agonism in neuropsychopharmacology.

Purpose: The prototypical TSPO radiotracer (R)-[¹¹C]PK11195 has been used in humans for more than thirty years to visualize neuroinflammation in several pathologies. Alternative radiotracers have been developed to improve signal-to-noise ratio and started to be tested clinically in 2008. Here we examined the scientific value of these “(R)-[¹¹C]PK11195 challengers” in clinical research to determine if they could supersede (R)-[¹¹C]PK11195.Methods: A systematic MEDLINE (PubMed) search was performed (up to end of year 2020) to extract publications reporting TSPO PET in patients with identified pathologies, excluding studies in healthy subjects and methodological studies.Results: Of the 288 publications selected, 152 used 13 challengers, and 142 used (R)-[¹¹C]PK11195. Over the last 20 years, the number of (R)-[¹¹C]PK11195 studies remained stable (6 ± 3 per year), but was surpassed by the total number of challenger studies for the last 6 years. In total, 3914 patients underwent a TSPO PET scan, and 47% (1851 patients) received (R)-[¹¹C]PK11195. The 2 main challengers were [¹¹C]PBR28 (24%—938 patients) and [¹⁸F]FEPPA (11%—429 patients). Only one-in-ten patients (11%—447) underwent 2 TSPO scans, among whom 40 (1%) were scanned with 2 different TSPO radiotracers.Conclusions: Generally, challengers confirmed disease-specific initial (R)-[¹¹C]PK11195 findings. However, while their better signal-to-noise ratio seems particularly useful in diseases with moderate and widespread neuroinflammation, most challengers present an allelic-dependent (Ala147Thr polymorphism) TSPO binding and genetic stratification is hindering their clinical implementation. As new challengers, insensitive to TSPO human polymorphism, are about to enter clinical evaluation, we propose this systematic review to be regularly updated (living review).