Measuring Drug Occupancy in the Absence of a Reference Region: The Lassen Plot Re-Visited
Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically boun...
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| Published in | Journal of cerebral blood flow and metabolism Vol. 30; no. 1; pp. 46 - 50 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London, England
SAGE Publications
01.01.2010
Nature Publishing Group Sage Publications Ltd |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (VND) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of VT alone to determine occupancy, together with an extension that does not require baseline data. |
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| AbstractList | Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (
V
T
) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (
V
ND
) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of
V
T
alone to determine occupancy, together with an extension that does not require baseline data. Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (V sub(T)) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (V sub(ND)) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of V sub(T) alone to determine occupancy, together with an extension that does not require baseline data. Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (VND) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of VT alone to determine occupancy, together with an extension that does not require baseline data. Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (V(T)) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (V(ND)) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of V(T) alone to determine occupancy, together with an extension that does not require baseline data. Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (V(T)) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (V(ND)) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of V(T) alone to determine occupancy, together with an extension that does not require baseline data.Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (V(T)) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (V(ND)) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of V(T) alone to determine occupancy, together with an extension that does not require baseline data. |
| Author | Rabiner, Eugenii A Laruelle, Marc Cunningham, Vincent J Gunn, Roger N Slifstein, Mark |
| Author_xml | – sequence: 1 givenname: Vincent J surname: Cunningham fullname: Cunningham, Vincent J email: vincent.j.cunningham@gsk.com – sequence: 2 givenname: Eugenii A surname: Rabiner fullname: Rabiner, Eugenii A – sequence: 3 givenname: Mark surname: Slifstein fullname: Slifstein, Mark – sequence: 4 givenname: Marc surname: Laruelle fullname: Laruelle, Marc – sequence: 5 givenname: Roger N surname: Gunn fullname: Gunn, Roger N |
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| Keywords | occupancy PET graphical analysis Nervous system diseases Central nervous system disease Positron emission tomography Cerebrovascular disease Cerebral disorder Emission tomography |
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| References_xml | – volume: 3 start-page: 1 year: 1983 end-page: 7 article-title: Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data publication-title: J Cereb Blood Flow Metab – volume: 16 start-page: 834 year: 1996 end-page: 40 article-title: Distribution volume ratios without blood sampling from graphical analysis of PET data publication-title: J Cereb Blood Flow Metab – volume: 11 start-page: S48 year: 2000 article-title: Receptor occupancy in absence of reference region publication-title: Neuroimage – volume: 22 start-page: 240 year: 2002 end-page: 4 article-title: Modified regression model for the logan plot publication-title: J Cereb Blood Flow Metab – volume: 34 start-page: 1450 year: 2007 end-page: 3 article-title: [ I]Epidepride binding to cerebellar dopamine D /D receptors is displaceable: implications for the use of cerebellum as a reference region publication-title: NeuroImage – volume: 10 start-page: 137 year: 1985 end-page: 42 article-title: Non-linear regression techniques in data analysis publication-title: Med Informatics – volume: 15 start-page: 152 year: 1995 end-page: 65 article-title: Benzodiazepine receptor quantification in humans using [11C]flumazenil and PET: application of the steady-state principle publication-title: J Cereb Blood Flow Metab – volume: 10 start-page: 740 year: 1990 end-page: 7 article-title: Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-[C-11]-methyl-(−)-Cocaine PET studies in human subjects publication-title: J Cereb Blood Flow Metab – volume: 23 start-page: 679 year: 2003 article-title: Definition of a reference region for PET [ C]diprenorphine studies publication-title: J Cereb Blood Flow Metab – volume: 24 start-page: 209 year: 2001 end-page: 29 article-title: Differential occupancy of somatodendritic and postsynaptic 5HT receptors by pindolol: a dose-occupancy study with [ C]WAY 100635 and positron emission tomography in humans publication-title: Neuropsychopharmacology – volume: 15 start-page: 217 year: 1984 end-page: 27 article-title: A quantitative model for the assessment of drug binding sites with positron emission tomography publication-title: Ann Neurol – volume: 22 start-page: 3557 year: 2003 end-page: 68 article-title: Estimation of kinetic parameters in graphical analysis of PET imaging data publication-title: Stat Med – volume: 27 start-page: 1533 year: 2007 end-page: 9 article-title: Consensus nomenclature for imaging of reversibly binding radioligands publication-title: J Cereb Blood Flow Metab – volume: 5 start-page: 584 year: 1985 end-page: 90 article-title: Graphical evaluation of blood-to-brain transfer constants from multiple- time uptake data. Generalizations publication-title: J Cereb Blood Flow Metab – volume: 41 start-page: 2083 year: 2000 end-page: 8 article-title: Effects of statistical noise on graphic analysis of PET neuroreceptor studies publication-title: J Nucl Med – volume: 11 start-page: S48 year: 2000 ident: bibr4-jcbfm.2009.190 publication-title: Neuroimage doi: 10.1016/S1053-8119(00)90982-0 – ident: bibr5-jcbfm.2009.190 doi: 10.1038/sj.jcbfm.9600493 – ident: bibr7-jcbfm.2009.190 doi: 10.1038/jcbfm.1990.127 – ident: bibr12-jcbfm.2009.190 doi: 10.1038/jcbfm.1983.1 – ident: bibr14-jcbfm.2009.190 doi: 10.1016/j.neuroimage.2006.11.003 – volume: 23 start-page: 679 year: 2003 ident: bibr1-jcbfm.2009.190 publication-title: J Cereb Blood Flow Metab – ident: bibr13-jcbfm.2009.190 doi: 10.1038/jcbfm.1985.87 – volume: 41 start-page: 2083 year: 2000 ident: bibr15-jcbfm.2009.190 publication-title: J Nucl Med – ident: bibr16-jcbfm.2009.190 doi: 10.1097/00004647-200202000-00012 – start-page: 499 volume-title: Quantification of brain function: tracer kinetics and image analysis in brain PET: proceedings of Brain PET '93 Akita Quantification of Brain Function, Akita, Japan, 29–31 May, 1993 year: 1993 ident: bibr2-jcbfm.2009.190 – ident: bibr11-jcbfm.2009.190 doi: 10.1002/sim.1562 – ident: bibr9-jcbfm.2009.190 doi: 10.1016/S0893-133X(00)00187-1 – ident: bibr3-jcbfm.2009.190 doi: 10.3109/14639238509010848 – ident: bibr6-jcbfm.2009.190 doi: 10.1038/jcbfm.1995.17 – ident: bibr10-jcbfm.2009.190 doi: 10.1002/ana.410150302 – ident: bibr8-jcbfm.2009.190 doi: 10.1097/00004647-199609000-00008 – reference: 11138696 - J Nucl Med. 2000 Dec;41(12):2083-8 – reference: 6822610 - J Cereb Blood Flow Metab. 1983 Mar;3(1):1-7 – reference: 7798333 - J Cereb Blood Flow Metab. 1995 Jan;15(1):152-65 – reference: 17519979 - J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9 – reference: 2384545 - J Cereb Blood Flow Metab. 1990 Sep;10(5):740-7 – reference: 4021648 - Med Inform (Lond). 1985 Apr-Jun;10(2):137-42 – reference: 11166513 - Neuropsychopharmacology. 2001 Mar;24(3):209-29 – reference: 6609679 - Ann Neurol. 1984 Mar;15(3):217-27 – reference: 14601019 - Stat Med. 2003 Nov 30;22(22):3557-68 – reference: 11823722 - J Cereb Blood Flow Metab. 2002 Feb;22(2):240-4 – reference: 8784228 - J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40 – reference: 17175177 - Neuroimage. 2007 Feb 15;34(4):1450-3 – reference: 4055928 - J Cereb Blood Flow Metab. 1985 Dec;5(4):584-90 |
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| SubjectTerms | Algorithms Biological and medical sciences Brain - diagnostic imaging Brief Communication Drug toxicity and drugs side effects treatment Humans Image Processing, Computer-Assisted Medical sciences Miscellaneous (drug allergy, mutagens, teratogens...) Monte Carlo Method Neurology Pharmaceutical Preparations - metabolism Pharmacology. Drug treatments Piperazines - metabolism Positron-Emission Tomography Pyridines - metabolism Receptor, Serotonin, 5-HT1A - drug effects Receptors, Drug - metabolism Serotonin Antagonists - metabolism Vascular diseases and vascular malformations of the nervous system |
| Title | Measuring Drug Occupancy in the Absence of a Reference Region: The Lassen Plot Re-Visited |
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