scholarly journals Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2451
Author(s):  
Paul Cumming ◽  
Milan Scheidegger ◽  
Dario Dornbierer ◽  
Mikael Palner ◽  
Boris B. Quednow ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Single Photon ◽  
Ex Vivo ◽  
Specific Binding ◽  
Photon Emission ◽  
Imaging Studies ◽  
Active Metabolites ◽  
Positron Emission ◽  
Imaging Research

Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood–brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.

scholarly journals Introduction to Infrared and Raman-Based Biomedical Molecular Imaging and Comparison with Other Modalities

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5547
Author(s):  
Carlos F. G. C. Geraldes
Keyword(s):  
Computed Tomography ◽  
Molecular Imaging ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Raman Imaging ◽  
Emission Computed Tomography ◽  
Label Free ◽  
Advantages And Disadvantages

Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional differences in imaged tissues at the cellular and molecular levels. Vibrational (infrared (IR) and Raman) imaging has rapidly emerged among the molecular imaging modalities available, due to its label-free combination of high spatial resolution with chemical specificity. This article presents the physical basis of vibrational spectroscopy and imaging, followed by illustration of their preclinical in vitro applications in body fluids and cells, ex vivo tissues and in vivo small animals and ending with a brief discussion of their clinical translation. After comparing the advantages and disadvantages of IR/Raman imaging with the other main modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography/single-photon emission-computed tomography (PET/SPECT), ultrasound (US) and photoacoustic imaging (PAI), the design of multimodal probes combining vibrational imaging with other modalities is discussed, illustrated by some preclinical proof-of-concept examples.

High non-specific binding of the β1-selective radioligand 2-125I-ICI-H

2003 ◽  
Vol 42 (04) ◽  
pp. 173-180 ◽  
Author(s):  
M. P. Law ◽  
K. Kopka ◽  
St. Wagner ◽  
S. Luthra ◽  
V. W. Pike ◽  
...  
Keyword(s):  
Specific Activity ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Radiochemical Yield ◽  
Emission Computed Tomography ◽  
Biodistribution Studies ◽  
Positron Emission

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

Radioligands for imaging myocardial α- and β-adrenoceptors

2003 ◽  
Vol 42 (01) ◽  
pp. 4-9 ◽  
Author(s):  
M. Schäfers ◽  
M. P. Law ◽  
T. Wichter ◽  
O. Schober ◽  
B. Riemann
Keyword(s):  
Single Photon ◽  
Heart Function ◽  
Specific Binding ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Relative Increase ◽  
Emission Tomography ◽  
Adrenoceptor Antagonist ◽  
Positron Emission ◽  
Cardiac Adrenoceptors

SummaryAlpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into α1-, α2- and β1-, β2-, β3-, β4-adrenoceptors. In cardiac disease, there is often a selective downregulation of β1-adrenoceptors associated with a relative increase in β2- and α1-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac α- and β-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective β-adrenoceptor antagonist [11C]CGP-12177 was used to quantify β-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [11C]CGP-12388, [18F]CGP-12388, [11C]carazolol and [18F]fluorocarazolol) are currently evaluated; β1-selective radioligands (e. g. [11C]CGP-26505, [11C]bisoprolol, [11C]HX-CH 44) and β2-selective radioligands (e. g. [11C]formoterol, [11C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET.Potential radioligands for imaging cardiac α1-adrenoceptors are based on prazosin. Whereas [11C]prazosin shows low specific binding to myocardium, its derivative [11C]GB67 looks more promising. The putative α2-adrenoceptor radioligand [11C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man.A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.

scholarly journals Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

2017 ◽  
Vol 1 ◽  
pp. 247054701771091 ◽  
Author(s):  
Margaret T. Davis ◽  
Sophie E. Holmes ◽  
Robert H. Pietrzak ◽  
Irina Esterlis
Keyword(s):  
Molecular Imaging ◽  
Chronic Stress ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Single Photon Emission ◽  
Major Depressive ◽  
Positron Emission ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress.

scholarly journals Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 182
Author(s):  
Ayman Abouzayed ◽  
Sara S. Rinne ◽  
Hamideh Sabahnoo ◽  
Jens Sörensen ◽  
Vladimir Chernov ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Computed Tomography ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Absorbed Dose ◽  
Single Step ◽  
Emission Computed Tomography

Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

scholarly journals Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jinhui Li ◽  
Jing Lu ◽  
You Zhou
Keyword(s):  
Molecular Imaging ◽  
Cardiac Disease ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Positron Emission ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Targeted Molecular Imaging

The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted99mTc-,123I-, and18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.

In vivo neuropharmacology of schizophrenia

1999 ◽  
Vol 174 (S38) ◽  
pp. 23-33 ◽  
Author(s):  
V. Bigliani ◽  
L. S. Pilowsky
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Emission Tomography ◽  
Binding Assays ◽  
Single Photon Emission ◽  
Positron Emission ◽  
The Brain ◽  
Major Target

Since the introduction of chlorpromazine in the 1950s, followed by the discovery (with in vitro receptor binding assays), in the mid-1970s, that antipsychotic drugs block a subtype of dopamine receptor (D2/D2-like) (Creese et al, 1976) and that affinity for these receptors appears to correlate directly with clinical potency for antipsychotics (Peroutka & Synder, 1980), the study of neurotransmitters and receptors has been a major target of schizophrenia research (Owens, 1996). In 1983, the first visualisation, by positron emission tomography (PET), of the binding of D2 dopamine receptors in the brain of a living human subject was reported (Wagner et al, 1983). Following this, the number of research studies using PET and single photon emission tomography (SPET) has increased enormously.

scholarly journals Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

2014 ◽  
Vol 34 (7) ◽  
pp. 1096-1103 ◽  
Author(s):  
Gregor Gryglewski ◽  
Rupert Lanzenberger ◽  
Georg S Kranz ◽  
Paul Cumming
Keyword(s):  
Molecular Imaging ◽  
Temporal Dynamics ◽  
Single Photon ◽  
Meta Analysis ◽  
Photon Emission ◽  
Strong Relationship ◽  
Emission Computed Tomography ◽  
Positron Emission ◽  
Sufficient Power ◽  
Severity Of Depression

The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g = −0.49; 95% CI: (−0.84, −0.14)) and amygdala (Hedges' g = −0.50; 95% CI: (−0.78, −0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g = −0.24, striatum: g = −0.32, and brainstem g = −0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations ( P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala ( P = 0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ˜10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.

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