Positron Emission Tomography for the Discovery of New Drugs in Psychiatry

Zimmer, Luc

doi:10.1021/acschemneuro.3c00036

Cited by 5 publications

(2 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be explained by the relatively low number of rats in each group ( n = 5). Moreover, our study used different individuals to compare 18 F-FDG uptake without and after pre-treatment by buprenorphine, which did not take full advantage of PET imaging as a minimally invasive procedure ( Lancelot and Zimmer, 2010 ; Zimmer, 2023 ). For future studies, comparison of the regional 18 F-FDG uptake in the same individuals, before and after administration of buprenorphine, would enable paired comparison with higher statistical power to better capture and compare the effects of buprenorphine across brain regions.…”

Section: Discussionmentioning

confidence: 99%

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

et al. 2023

View full text Add to dashboard Cite

AimBuprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids in vivo. We hypothesized that the CNS effects of acute buprenorphine could be monitored through changes in regional brain glucose metabolism, assessed using 18F-FDG microPET in rats.Materials and methodsFirst, level of receptor occupancy associated with a single dose of buprenorphine (0.1 mg/kg, s.c) was investigated through blocking experiments using 11C-buprenorphine PET imaging. Behavioral study using the elevated plus-maze test (EPM) was performed to assess the impact of the selected dose on anxiety and also locomotor activity. Then, brain PET imaging using 18F-FDG was performed 30 min after injection of unlabeled buprenorphine (0.1 mg/kg, s.c) vs. saline. Two different 18F-FDG PET acquisition paradigms were compared: (i) 18F-FDG injected i.v. under anesthesia and (ii) 18F-FDG injected i.p. in awake animals to limit the impact of anesthesia.ResultsThe selected dose of buprenorphine fully blocked the binding of 11C-buprenorphine in brain regions, suggesting complete receptor occupancy. This dose had no significant impact on behavioral tests used, regardless of the anesthetized/awake handling paradigm. In anesthetized rats, injection of unlabeled buprenorphine decreased the brain uptake of 18F-FDG in most brain regions except in the cerebellum which could be used as a normalization region. Buprenorphine treatment significantly decreased the normalized brain uptake of 18F-FDG in the thalamus, striatum and midbrain (p < 0.05), where binding of 11C-buprenorphine was the highest. The awake paradigm did not improve sensitivity and impact of buprenorphine on brain glucose metabolism could not be reliably estimated.ConclusionBuprenorphine (0.1 mg/kg, s.c) combined with 18F-FDG brain PET in isoflurane anesthetized rats provides a simple pharmacological imaging challenge to investigate the CNS effects of full receptor occupancy by this partial mu-OR agonist. Sensitivity of the method was not improved in awake animals. This strategy may be useful to investigate de desensitization of mu-OR associated with opioid tolerance in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have emerged as powerful non-invasive molecular imaging techniques in detecting biochemical processes, and have wide applications in drug development and clinic diagnosis [8][9][10]. Molecular imaging with radiolabeled probes offers greater tissue penetration, better quantification, and facile animal-to-human translatability.…”

Section: Radiolabeled Imaging Probesmentioning

confidence: 99%

Small molecule probes for the specific imaging of monoamine oxidase A and monoamine oxidase B

Fang,

Chen,

Yang

2024

iRADIOLOGY

View full text Add to dashboard Cite

Monoamine oxidases (MAOs) are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system. Furthermore, expression of MAOs is associated with the functions of peripheral organs. Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases, heart failure, metabolic disorders, and cancers. Monoamine oxidases have two isoenzymes, namely, monoamine oxidase A (MAO‐A) and monoamine oxidase B (MAO‐B). Therefore, the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in‐depth understanding of their functions in biological systems, and for further promoting the clinical diagnosis and treatment of MAO‐related diseases. This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO‐A and MAO‐B, including radiolabeled probes, fluorescent probes, and a 19F magnetic resonance imaging probe. In addition, applications of these probes for detecting MAO expression levels in cells, tissues, animal models, and patients are described. Finally, the challenges and perspectives of developing novel MAO imaging probes are also highlighted.

show abstract

Structure-Affinity-Pharmacokinetics Relationships of Novel ¹⁸F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging

Ishizaka,

Watanabe,

Ono

2024

J. Med. Chem.

View full text Add to dashboard Cite

The orexin 1 receptor (OX1R) has been suggested to be involved in the reward and autonomic nervous systems. Positron emission tomography (PET) of OX1R contributes to elucidating its role and developing new drugs. However, there are no useful PET probes for in vivo imaging of OX1R. Here, we newly designed and synthesized 18 F-labeled 1,4-diazepane derivatives and evaluated their utilities as OX1R PET probes. In particular, BTF showed high and selective binding affinity for OX1R. In a biodistribution study using normal mice, [ 18 F]BTF exhibited brain uptake, and radioactivity in the brain was significantly decreased by preinjection of unlabeled BTF. In a PET/CT study, it was suggested that [ 18 F]BTF has the potential to visualize highexpression regions of OX1R in the normal mouse brain. Collectively, [ 18 F]BTF has the fundamental features of an OX1R PET probe, and further studies may lead to the development of more useful probes.

show abstract

Positron Emission Tomography for the Discovery of New Drugs in Psychiatry

Cited by 5 publications

References 6 publications

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

Small molecule probes for the specific imaging of monoamine oxidase A and monoamine oxidase B

Structure-Affinity-Pharmacokinetics Relationships of Novel ¹⁸F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging

Contact Info

Product

Resources

About

Positron Emission Tomography for the Discovery of New Drugs in Psychiatry

Cited by 5 publications

References 6 publications

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain

Small molecule probes for the specific imaging of monoamine oxidase A and monoamine oxidase B

Structure-Affinity-Pharmacokinetics Relationships of Novel 18F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging

Contact Info

Product

Resources

About

Structure-Affinity-Pharmacokinetics Relationships of Novel ¹⁸F-Labeled 1,4-Diazepane Derivatives for Orexin 1 Receptor Imaging