Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 4/2013

01-08-2013 | Research Article

Suitability of [18F]Altanserin and PET to Determine 5-HT2A Receptor Availability in the Rat Brain: In Vivo and In Vitro Validation of Invasive and Non-Invasive Kinetic Models

Authors: Tina Kroll, David Elmenhorst, Andreas Matusch, Franziska Wedekind, Angela Weisshaupt, Simone Beer, Andreas Bauer

Published in: Molecular Imaging and Biology | Issue 4/2013

Login to get access

Abstract

Purpose

While the selective 5-hydroxytryptamine type 2a receptor (5-HT2AR) radiotracer [18F]altanserin is well established in humans, the present study evaluated its suitability for quantifying cerebral 5-HT2ARs with positron emission tomography (PET) in albino rats.

Procedures

Ten Sprague Dawley rats underwent 180 min PET scans with arterial blood sampling. Reference tissue methods were evaluated on the basis of invasive kinetic models with metabolite-corrected arterial input functions. In vivo 5-HT2AR quantification with PET was validated by in vitro autoradiographic saturation experiments in the same animals.

Result

Overall brain uptake of [18F]altanserin was reliably quantified by invasive and non-invasive models with the cerebellum as reference region shown by linear correlation of outcome parameters. Unlike in humans, no lipophilic metabolites occurred so that brain activity derived solely from parent compound. PET data correlated very well with in vitro autoradiographic data of the same animals.

Conclusion

[18F]Altanserin PET is a reliable tool for in vivo quantification of 5-HT2AR availability in albino rats. Models based on both blood input and reference tissue describe radiotracer kinetics adequately. Low cerebral tracer uptake might, however, cause restrictions in experimental usage.
Literature
1.
Elmenhorst D, Kroll T, Matusch A, Bauer A (2012) Sleep Deprivation Increases Cerebral Serotonin 2A Receptor Binding in Humans. Sleep 35:1615–1623PubMed
2.
Frokjaer VG, Mortensen EL, Nielsen FA et al (2008) Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder. Biol Psychiatry 63:569–576PubMedCrossRef
3.
Hurlemann R, Matusch A, Kuhn KU et al (2008) 5-HT2A receptor density is decreased in the at-risk mental state. Psychopharmacology 195:579–590PubMedCrossRef
4.
Pazos A, Cortés R, Palacios JM (1985) Quantitative Autoradiographic Mapping of Serotonin Receptors in the Rat Brain. II. Serotonin-2 Receptors. Brain Res 346:231–249PubMedCrossRef
5.
Kristiansen H, Elfving B, Plenge P et al (2005) Binding Characteristics of the 5-HT2A Receptor Antagonists Altanserin and MDL 100907. Synapse 58:249–257PubMedCrossRef
6.
Haugbol S, Pinborg LH, Arfan HM et al (2007) Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach. Eur J Nucl Med Mol Imaging 34:910–915PubMedCrossRef
7.
Pinborg LH, Adams KH, Svarer C et al (2003) Quantification of 5-HT2A Receptors in the Human Brain Using [18F]Altanserin-PET and the Bolus/Infusion Approach. J Cereb Blood Flow Metab 23:985–996PubMedCrossRef
8.
Tan PZ, Baldwin RM, Van Dyck CH et al (1999) Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [18F]altanserin in human and rodent. Nucl Med Biol 26:601–608PubMedCrossRef
9.
Riss PJ, Hong YT, Williamson D et al (2011) Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling. J Cereb Blood Flow Metab 31:2334–2342PubMedCrossRef
10.
McDermott C, Kelly JP (2008) Comparison of the behavioural pharmacology of the Lister-Hooded with 2 commonly utilised albino rat strains. Prog Neuropsychopharmacol Biol Psychiatry 32:1816–1823PubMedCrossRef
11.
Parsons MJ, Benca RM, Brownfield MS, Behan M (2001) Age-associated changes in the serotonergic system in rat superior colliculus and pretectum. Brain Res Bull 55:435–444PubMedCrossRef
12.
Hamacher K, Coenen HH (2006) No-carrier-added nucleophilic 18F-labelling in an electrochemical cell exemplified by the routine production of [18F]altanserin. Appl Radiat Isot 64:989–994PubMedCrossRef
13.
Maeshima T, Shutoh F, Hamada S et al (1998) Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells. Neurosci Lett 252:72–74PubMedCrossRef
14.
Innis RB, Cunningham VJ, Delforge J et al (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539PubMedCrossRef
15.
Gunn RN, Gunn SR, Cunningham VJ (2001) Positron Emission Tomography Compartmental Models. J Cereb Blood Flow Metab 21:635–652PubMedCrossRef
16.
Adam J, Elleaume H, Le Duc G et al (2003) Absolute cerebral blood volume and blood flow measurements based on synchrotron radiation quantitative computed tomography. J Cereb Blood Flow Metab 23:499–512PubMedCrossRef
17.
Logan J, Fowler JS, Volkow ND et al (1990) Graphical Analysis of Reversible Radioligand Binding from Time-Activity Measurements Applied to [N-11C-methyl]-( − )-Cocaine PET Studies in Human Subjects. J Cereb Blood Flow Metab 10:740–747PubMedCrossRef
18.
Ichise M, Toyama H, Innis RB, Carson RE (2002) Strategies to improve neuroreceptor parameter estimation by linear regression analysis. J Cereb Blood Flow Metab 22:1271–1281PubMedCrossRef
19.
Lammertsma AA, Hume SP (1996) Simplified Reference Tissue Model for PET Receptor Studies. NeuroImage 4:153–158PubMedCrossRef
20.
Wu Y, Carson RE (2002) Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab 22:1440–1452PubMedCrossRef
21.
Logan J, Fowler JS, Volkow ND et al (1996) Distribution Volume Ratios Without Blood Sampling from Graphical Analysis of PET Data. J Cereb Blood Flow Metab 16:834–840PubMedCrossRef
22.
Ichise M, Loiw JS, Lu JQ et al (2003) Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain. J Cereb Blood Flow Metab 23:1096–1112PubMedCrossRef
23.
Mintun MA, Raichle ME, Kilbourn MR, Wooton GF, Welch MJ (1984) A Quantitative Model for the In Vivo Assessment of Drug Binding Sites with Positron Emission Tomography. Ann Neurol 15:217–227PubMedCrossRef
24.
López-Giménez JF, Mengod G, Palacios JM, Vilaró MT (1997) Selective visualization of rat brain 5-HT2A receptors by autoradiography with [3H]MDL 100,907. Naunyn-Schmiedeberg’s Arch Pharmacol 356:446–454CrossRef
25.
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego
26.
Chen F, Lawrence AJ (2003) The effects of antidepressant treatment on serotonergic and dopaminergic systems in Fawn–Hooded rats: a quantitative autoradiography study. Brain Res 976:22–29PubMedCrossRef
27.
Sato H, Skelin I, Diksic M (2010) Chronic buspirone treatment decreases 5-HT1B receptor densities and the serotonin transporter but increases the density of 5-HT2A receptors in the bulbectomized rat model of depression: an autoradiographic study. Brain Res 1345:28–40PubMedCrossRef
28.
Syvänen S, Lindhe Ö, Palner M et al (2009) Species Differences in Blood–brain Barrier Transport of Three Positron Emission Tomography Radioligands with Emphasis on P- Glycoprotein Transport. Drug Metab Dispos 37:635–643PubMedCrossRef
29.
Preece MA, Dalley JW, Theobald DEH, Robbins TW, Reynolds GP (2004) Region Specific Changes in Forebrain 5-Hydroxytryptamine1A and 5-Hydroxytryptamine2A Receptors in isolation-reared Rats: An in vitro autoradiographic Study. Neuroscience 123:725–732PubMedCrossRef
30.
Hamada S, Senzaki K, Hamguchi-Hamada K et al (1998) Localization of 5-HT2A Receptor in rat cerebral cortex and olfactory system revealed by immunohistochemistry using two antibodies raised in rabbit and chicken. Mol Brain Res 54:199–211PubMedCrossRef
31.
Xu T, Pandey SC (2000) Cellular localization of serotonin2A (5HT2A) receptors in the rat brain. Brain Res Bull 51:499–505PubMedCrossRef
32.
Biver F, Lotstra F, Monclus M et al (1997) In vivo binding of [18F]altanserin to rat brain 5HT2 receptors: a film and electronic autoradiographic study. Nucl Med Biol 24:357–360PubMedCrossRef
33.
Elmenhorst D, Minuzzi L, Aliaga A et al (2010) In vivo and in vitro validation of reference tissue models for the mGluR5 ligand [11C]ABP688. J Cereb Blood Flow Metab 30:1538–1549PubMedCrossRef
34.
Gallezot JD, Nabulsi N, Neumeister A et al (2010) Kinetic modeling of the serotonin 5-HT1B receptor radioligand [11C]P943 in humans. J Cereb Blood Flow Metab 30:196–210PubMedCrossRef
35.
Meyer PT, Bhagwagar Z, Cowen PJ et al (2010) Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses. NeuroImage 50:984–993PubMedCrossRef
36.
Forutan F, Estalj S, Beu M et al (2002) Distribution of 5HT2A receptors in the human brain: comparison of data in vivo and post mortem. Nuklearmedizin 41:197–201PubMed
37.
Strome EM, Cepeda IL, Sossi V, Doudet DJ (2006) Evaluation of the Integrity of the Dopamine System in a Rodent Model of Parkinson’s Disease: Small Animal Positron Emission Tomography Compared to Behavioral Assessment and Autoradiography. Mol Imaging Biol 8:292–299PubMedCrossRef
38.
Fischer K, Sossi V, von Ameln-Mayerhofer A, Reischl G, Pichler BJ (2012) In vivo quantification of dopamine transporters in mice with unilateral 6-OHDA lesions using [11C]methylphenidate and PET. NeuroImage 59:2413–2422PubMedCrossRef
39.
Manook A, Yousefi BH, Willuweit A et al (2012) Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer’s Disease. PLoS One 7:e31310PubMedCrossRef
Metadata
Title
Suitability of [18F]Altanserin and PET to Determine 5-HT2A Receptor Availability in the Rat Brain: In Vivo and In Vitro Validation of Invasive and Non-Invasive Kinetic Models
Authors
Tina Kroll
David Elmenhorst
Andreas Matusch
Franziska Wedekind
Angela Weisshaupt
Simone Beer
Andreas Bauer
Publication date
01-08-2013
Publisher
Springer US
Published in
Molecular Imaging and Biology / Issue 4/2013
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-013-0621-3

Other articles of this Issue 4/2013

Molecular Imaging and Biology 4/2013 Go to the issue

Research Article

Evaluation of Inflammatory Response to Acute Ischemia Using Near-Infrared Fluorescent Reactive Oxygen Sensors

Research Article

Evaluation of 89Zr-rituximab Tracer by Cerenkov Luminescence Imaging and Correlation with PET in a Humanized Transgenic Mouse Model to Image NHL

Brief Article

Whole-Body Biodistribution and Radiation Dosimetry of the Cannabinoid Type 2 Receptor Ligand [11C]-NE40 in Healthy Subjects

Research Article

Improved Derivation of Input Function in Dynamic Mouse [18F]FDG PET Using Bladder Radioactivity Kinetics

Research Article

MRI of ICAM-1 Upregulation After Stroke: the Importance of Choosing the Appropriate Target-Specific Particulate Contrast Agent

Letter to the Editor

Dynamic Changes of 18F-FDG Uptake in Normal Lung: Probing a Predictive Model Analysis