Skip to main content
Top
Published in: Molecular Imaging and Biology 6/2009

Open Access 01-11-2009 | Research Article

[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Authors: Janine Doorduin, Hans C. Klein, Rudi A. Dierckx, Michelle James, Michael Kassiou, Erik F. J. de Vries

Published in: Molecular Imaging and Biology | Issue 6/2009

Login to get access

Abstract

Background

Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [11C]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [11C]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [11C]-DPA-713 and [18F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis.

Materials and Methods

Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [11C]-(R)-PK11195, [11C]-DPA-713, and [18F]-DPA-714.

Results

Uptake of [11C]-DPA-713 in infected brain areas was comparable to that of [11C]-(R)-PK11195, but [11C]-DPA-713 showed lower non-specific binding. Non-specific uptake of [18F]-DPA-714 was lower than that of [11C]-(R)-PK11195. In the infected brain, total [18F]-DPA-714 uptake was lower than that of [11C]-(R)-PK11195, with comparable specific uptake.

Conclusions

[11C]-DPA-713 may be more suitable for visualizing mild inflammation than [11C]-(R)-PK11195. In addition, the fact that [18F]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting.
Literature
1.
go back to reference World Health Organization (2006) Neurological disorders; public health challenges. WHO, Geneva World Health Organization (2006) Neurological disorders; public health challenges. WHO, Geneva
2.
go back to reference Nakajima K, Kohsaka S (2004) Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord 4(1):65–84CrossRefPubMed Nakajima K, Kohsaka S (2004) Microglia: neuroprotective and neurotrophic cells in the central nervous system. Curr Drug Targets Cardiovasc Haematol Disord 4(1):65–84CrossRefPubMed
3.
go back to reference Davalos D, Grutzendler J, Yang G et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752–758CrossRefPubMed Davalos D, Grutzendler J, Yang G et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752–758CrossRefPubMed
4.
go back to reference Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318CrossRefPubMed Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318CrossRefPubMed
5.
go back to reference Gerhard A, Neumaier B, Elitok E et al (2000) In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport 11(13):2957–2960CrossRefPubMed Gerhard A, Neumaier B, Elitok E et al (2000) In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport 11(13):2957–2960CrossRefPubMed
6.
go back to reference Gerhard A, Schwarz J, Myers R, Wise R, Banati RB (2005) Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study. Neuroimage 24(2):591–595CrossRefPubMed Gerhard A, Schwarz J, Myers R, Wise R, Banati RB (2005) Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study. Neuroimage 24(2):591–595CrossRefPubMed
7.
go back to reference Pappata S, Levasseur M, Gunn RN et al (2000) Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK1195. Neurology 55(7):1052–1054PubMed Pappata S, Levasseur M, Gunn RN et al (2000) Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK1195. Neurology 55(7):1052–1054PubMed
8.
go back to reference Ramsay SC, Weiller C, Myers R et al (1992) Monitoring by PET of macrophage accumulation in brain after ischaemic stroke. Lancet 339(8800):1054–1055CrossRefPubMed Ramsay SC, Weiller C, Myers R et al (1992) Monitoring by PET of macrophage accumulation in brain after ischaemic stroke. Lancet 339(8800):1054–1055CrossRefPubMed
9.
go back to reference Banati RB, Newcombe J, Gunn RN et al (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123:2321–2337CrossRefPubMed Banati RB, Newcombe J, Gunn RN et al (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123:2321–2337CrossRefPubMed
10.
go back to reference Debruyne JC, Versijpt J, Van Laere KJ et al (2003) PET visualization of microglia in multiple sclerosis patients using [11C]PK11195. Eur J Neurol 10(3):257–264CrossRefPubMed Debruyne JC, Versijpt J, Van Laere KJ et al (2003) PET visualization of microglia in multiple sclerosis patients using [11C]PK11195. Eur J Neurol 10(3):257–264CrossRefPubMed
11.
go back to reference Versijpt J, Debruyne JC, Van Laere KJ et al (2005) Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 11(2):127–134CrossRefPubMed Versijpt J, Debruyne JC, Van Laere KJ et al (2005) Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 11(2):127–134CrossRefPubMed
12.
go back to reference Vowinckel E, Reutens D, Becher B et al (1997) PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res 50(2):345–353CrossRefPubMed Vowinckel E, Reutens D, Becher B et al (1997) PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res 50(2):345–353CrossRefPubMed
13.
go back to reference Cagnin A, Myers R, Gunn RN et al (2001) In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion. Brain 124(Pt 10):2014–2027CrossRefPubMed Cagnin A, Myers R, Gunn RN et al (2001) In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion. Brain 124(Pt 10):2014–2027CrossRefPubMed
14.
go back to reference Gerhard A, Pavese N, Hotton G et al (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis 21(2):404–412CrossRefPubMed Gerhard A, Pavese N, Hotton G et al (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis 21(2):404–412CrossRefPubMed
15.
go back to reference Ouchi Y, Yoshikawa E, Sekine Y et al (2005) Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann Neurol 57(2):168–175CrossRefPubMed Ouchi Y, Yoshikawa E, Sekine Y et al (2005) Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann Neurol 57(2):168–175CrossRefPubMed
16.
go back to reference Cagnin A, Brooks DJ, Kennedy AM et al (2001) In-vivo measurement of activated microglia in dementia. Lancet 358(9280):461–467CrossRefPubMed Cagnin A, Brooks DJ, Kennedy AM et al (2001) In-vivo measurement of activated microglia in dementia. Lancet 358(9280):461–467CrossRefPubMed
17.
go back to reference Cagnin A, Rossor M, Sampson EL, Mackinnon T, Banati RB (2004) In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol 56(6):894–897CrossRefPubMed Cagnin A, Rossor M, Sampson EL, Mackinnon T, Banati RB (2004) In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol 56(6):894–897CrossRefPubMed
18.
go back to reference Groom GN, Junck L, Foster NL, Frey KA, Kuhl DE (1995) PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. J Nucl Med 36(12):2207–2210PubMed Groom GN, Junck L, Foster NL, Frey KA, Kuhl DE (1995) PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. J Nucl Med 36(12):2207–2210PubMed
19.
go back to reference James ML, Fulton RR, Vercouille J et al (2007) DPA-714 a new translocator protein (18 kDa) ligand: synthesis, radiofluorination and pharmacological characterisation. J Label Compd Radiopharm 50(Supplement 1):S25 James ML, Fulton RR, Vercouille J et al (2007) DPA-714 a new translocator protein (18 kDa) ligand: synthesis, radiofluorination and pharmacological characterisation. J Label Compd Radiopharm 50(Supplement 1):S25
20.
go back to reference James ML, Fulton RR, Vercoullie J et al (2008) DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med 49(5):814–822CrossRefPubMed James ML, Fulton RR, Vercoullie J et al (2008) DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization. J Nucl Med 49(5):814–822CrossRefPubMed
21.
go back to reference Selleri S, Bruni F, Costagli C et al (2001) 2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands. Bioorg Med Chem 9(10):2661–2671CrossRefPubMed Selleri S, Bruni F, Costagli C et al (2001) 2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands. Bioorg Med Chem 9(10):2661–2671CrossRefPubMed
22.
go back to reference James ML, Fulton RR, Henderson DJ et al (2005) Synthesis and in vivo evaluation of a novel peripheral benzodiazepine receptor PET radioligand. Bioorg Med Chem 13(22):6188–6194CrossRefPubMed James ML, Fulton RR, Henderson DJ et al (2005) Synthesis and in vivo evaluation of a novel peripheral benzodiazepine receptor PET radioligand. Bioorg Med Chem 13(22):6188–6194CrossRefPubMed
23.
go back to reference Boutin H, Chauveau F, Thominiaux C et al (2007) 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med 48(4):573–581CrossRefPubMed Boutin H, Chauveau F, Thominiaux C et al (2007) 11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation. J Nucl Med 48(4):573–581CrossRefPubMed
24.
go back to reference Larsen P, Ulin J, Dahlstrom K, Jensen M (1997) Synthesis of [C-11]iodomethane by iodination of [C-11]methane. Appl Radiat Isot 48(2):153–157CrossRef Larsen P, Ulin J, Dahlstrom K, Jensen M (1997) Synthesis of [C-11]iodomethane by iodination of [C-11]methane. Appl Radiat Isot 48(2):153–157CrossRef
25.
go back to reference Kurumaji A, Kaneko K, Toru M (1996) Effects of chronic treatment with haloperidol on [3H]PK 11195 binding in the rat brain and peripheral tissues. Neuropharmacology 35(8):1075–1079CrossRefPubMed Kurumaji A, Kaneko K, Toru M (1996) Effects of chronic treatment with haloperidol on [3H]PK 11195 binding in the rat brain and peripheral tissues. Neuropharmacology 35(8):1075–1079CrossRefPubMed
26.
go back to reference Steiner J, Mawrin C, Ziegeler A et al (2006) Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathol 112(3):305–316CrossRefPubMed Steiner J, Mawrin C, Ziegeler A et al (2006) Distribution of HLA-DR-positive microglia in schizophrenia reflects impaired cerebral lateralization. Acta Neuropathol 112(3):305–316CrossRefPubMed
27.
go back to reference Itzhaki R (2004) Herpes simplex virus type 1, apolipoprotein E and Alzheimer’ disease. Herpes 11(Suppl 2):77A–82APubMed Itzhaki R (2004) Herpes simplex virus type 1, apolipoprotein E and Alzheimer’ disease. Herpes 11(Suppl 2):77A–82APubMed
28.
go back to reference DeLano RM, Mallery SR (1998) Stress-related modulation of central nervous system immunity in a murine model of herpes simplex encephalitis. J Neuroimmunol 89(1–2):51–58CrossRefPubMed DeLano RM, Mallery SR (1998) Stress-related modulation of central nervous system immunity in a murine model of herpes simplex encephalitis. J Neuroimmunol 89(1–2):51–58CrossRefPubMed
29.
go back to reference Esiri MM, Drummond CW, Morris CS (1995) Macrophages and microglia in HSV-1 infected mouse brain. J Neuroimmunol 62(2):201–205CrossRefPubMed Esiri MM, Drummond CW, Morris CS (1995) Macrophages and microglia in HSV-1 infected mouse brain. J Neuroimmunol 62(2):201–205CrossRefPubMed
30.
go back to reference Barnett EM, Cassell MD, Perlman S (1993) Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb. Neuroscience 57(4):1007–1025CrossRefPubMed Barnett EM, Cassell MD, Perlman S (1993) Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb. Neuroscience 57(4):1007–1025CrossRefPubMed
31.
go back to reference Mori I, Goshima F, Ito H et al (2005) The vomeronasal chemosensory system as a route of neuroinvasion by herpes simplex virus. Virology 334(1):51–58CrossRefPubMed Mori I, Goshima F, Ito H et al (2005) The vomeronasal chemosensory system as a route of neuroinvasion by herpes simplex virus. Virology 334(1):51–58CrossRefPubMed
33.
go back to reference Chauveau F, van Camp N, Damont A et al (2008) [18F]DPA-714: a highly promising fluorine-18-labelled tracer for neuroinflammation imaging. World Molecular Imaging Congress Chauveau F, van Camp N, Damont A et al (2008) [18F]DPA-714: a highly promising fluorine-18-labelled tracer for neuroinflammation imaging. World Molecular Imaging Congress
Metadata
Title
[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis
Authors
Janine Doorduin
Hans C. Klein
Rudi A. Dierckx
Michelle James
Michael Kassiou
Erik F. J. de Vries
Publication date
01-11-2009
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 6/2009
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-009-0211-6

Other articles of this Issue 6/2009

Molecular Imaging and Biology 6/2009 Go to the issue

Letter to the Editor

Letter to the Editor