PET Imaging of Beta-Adrenoceptors in Human Brain: A Realistic Goal or a Mirage?

Abstract

Beta-adrenoceptors are predominantly located in the cerebral cortex, nucleus accumbens and striatum. At lower densities, they are also present in amygdala, hippocampus and cerebellum. Beta-2 sites regulate glial proliferation during ontogenic development, after trauma and in neurodegenerative diseases. The densities of beta-1 adrenoceptors are changed by stress, in several mood disorders (depression, excessive hostility, schizophrenia) and during treatment of patients with antidepressants. A technique for beta-adrenoceptor imaging in the human brain is not yet available. Although 24 (ant)agonists have been labeled with either (11)C or (18)F and some of these are successful myocardial imaging agents, only two (S-1'-(18)F-fluorocarazolol and S-1'-(18)F-fluoroethylcarazolol) could actually visualize beta-adrenoceptors within the central nervous system. Unfortunately, these radiopharmaceuticals showed a positive Ames test. They may be mutagenic and cannot be employed for human studies. Screening of more than 150 beta-blockers described in the literature yields only two compounds (exaprolol and L643,717) which can still be radiolabeled and evaluated for beta-adenoceptor imaging. However, other imaging techniques could be examined. Cerebral beta-adrenoceptors might be labeled after temporary opening of the blood-brain barrier (BBB) and simultaneous administration of a hydrophilic ligand such as S-(11)C-CGP12388. Another approach to target beta-adrenoceptor ligands to the CNS is esterification of a myocardial imaging agent (such as (11)C-CGP12177), resulting in a lipophilic prodrug which can cross the BBB and is split by tissue esterases. BBB opening is not feasible in healthy subjects, but the prodrug approach may be successful and deserves to be explored.

Association between Depression, Pressure Pain Sensitivity, Stress and Autonomous Nervous System Function in Stable Ischemic Heart Disease: Impact of Beta-Adrenergic Receptor Blockade

“…In order to study an association that includes a reduction of the depression score, the reduction may be minor or absent if the depression score is within normal range at baseline. This has already been discussed in a comprehensive manner [26]. In the present study, the effects of beta-blockers that are observed in the group as a whole are more pronounced when analysed in the subgroup of patients with an elevated depression score at baseline.…”

“…This may be compared to the minimum clinical relevant antidepressant effect for pharmacological treatment of patients with overt depression (e.g. MDI score ≥ 20 at baseline) which was 0.3 according to the US Federal Drug Administration [26]. As such, it may be concluded that the achieved clinical effect size by this non-pharmacological intervention was clinically relevant for IHD patients in general, and even more so for the patients with an elevated depression score.…”

Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway

“…The antidepressant effect exerted by the drug desipramine determined in an unpredictable chronic mild stress model in mice was reversed by propranolol [25]. Furthermore, according to several studies, β-adrenoceptors may be involved in the action of antidepressants [26][27][28][29].…”

[18F]Fluoroalkyl Agents: Synthesis, Reactivity and Application for Development of PET Ligands in Molecular Imaging

“…in the brain, myocardium, tumor and other regions or organs . Some reviews concerning promising PET probes including the [ 18 F]fluoroalkyl ligands for molecular imaging have been published [79][80][81]. [13,26,[92][93][94][95][96][97][98][99].…”