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Published in: EJNMMI Research 1/2012

Open Access 01-12-2012 | Original research

Reproducibility of quantitative (R)-[11C]verapamil studies

Authors: Daniëlle ME van Assema, Mark Lubberink, Ronald Boellaard, Robert C Schuit, Albert D Windhorst, Philip Scheltens, Bart NM van Berckel, Adriaan A Lammertsma

Published in: EJNMMI Research | Issue 1/2012

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Abstract

Background

P-glycoprotein [Pgp] dysfunction may be involved in neurodegenerative diseases, such as Alzheimer's disease, and in drug resistant epilepsy. Positron emission tomography using the Pgp substrate tracer (R)-[11C]verapamil enables in vivo quantification of Pgp function at the human blood-brain barrier. Knowledge of test-retest variability is important for assessing changes over time or after treatment with disease-modifying drugs. The purpose of this study was to assess reproducibility of several tracer kinetic models used for analysis of (R)-[11C]verapamil data.

Methods

Dynamic (R)-[11C]verapamil scans with arterial sampling were performed twice on the same day in 13 healthy controls. Data were reconstructed using both filtered back projection [FBP] and partial volume corrected ordered subset expectation maximization [PVC OSEM]. All data were analysed using single-tissue and two-tissue compartment models. Global and regional test-retest variability was determined for various outcome measures.

Results

Analysis using the Akaike information criterion showed that a constrained two-tissue compartment model provided the best fits to the data. Global test-retest variability of the volume of distribution was comparable for single-tissue (6%) and constrained two-tissue (9%) compartment models. Using a single-tissue compartment model covering the first 10 min of data yielded acceptable global test-retest variability (9%) for the outcome measure K 1. Test-retest variability of binding potential derived from the constrained two-tissue compartment model was less robust, but still acceptable (22%). Test-retest variability was comparable for PVC OSEM and FBP reconstructed data.

Conclusion

The model of choice for analysing (R)-[11C]verapamil data is a constrained two-tissue compartment model.
Appendix
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Literature
1.
go back to reference Schinkel AH: P-glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev 1999, 36: 179–194. 10.1016/S0169-409X(98)00085-4PubMedCrossRef Schinkel AH: P-glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev 1999, 36: 179–194. 10.1016/S0169-409X(98)00085-4PubMedCrossRef
2.
go back to reference Demeule M, Labelle M, Regina A, Berthelet F, Beliveau R: Isolation of endothelial cells from brain, lung, and kidney: expression of the multidrug resistance P-glycoprotein isoforms. Biochem Biophys Res Commun 2001, 281: 827–834. 10.1006/bbrc.2001.4312PubMedCrossRef Demeule M, Labelle M, Regina A, Berthelet F, Beliveau R: Isolation of endothelial cells from brain, lung, and kidney: expression of the multidrug resistance P-glycoprotein isoforms. Biochem Biophys Res Commun 2001, 281: 827–834. 10.1006/bbrc.2001.4312PubMedCrossRef
3.
go back to reference Fromm MF: Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci 2004, 25: 423–429. 10.1016/j.tips.2004.06.002PubMedCrossRef Fromm MF: Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci 2004, 25: 423–429. 10.1016/j.tips.2004.06.002PubMedCrossRef
4.
go back to reference de Lange EC: Potential role of ABC transporters as a detoxification system at the blood-CSF barrier. Adv Drug Deliv Rev 2004, 56: 1793–1809. 10.1016/j.addr.2004.07.009PubMedCrossRef de Lange EC: Potential role of ABC transporters as a detoxification system at the blood-CSF barrier. Adv Drug Deliv Rev 2004, 56: 1793–1809. 10.1016/j.addr.2004.07.009PubMedCrossRef
5.
go back to reference Loscher W, Potschka H: Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2005, 2: 86–98. 10.1602/neurorx.2.1.86PubMedCentralPubMedCrossRef Loscher W, Potschka H: Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2005, 2: 86–98. 10.1602/neurorx.2.1.86PubMedCentralPubMedCrossRef
6.
go back to reference Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W, Kunert-Keil C, Walker LC, Warzok RW: Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 2002, 12: 535–541. 10.1097/00008571-200210000-00005PubMedCrossRef Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W, Kunert-Keil C, Walker LC, Warzok RW: Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 2002, 12: 535–541. 10.1097/00008571-200210000-00005PubMedCrossRef
7.
go back to reference Vogelgesang S, Glatzel M, Walker LC, Kroemer HK, Aguzzi A, Warzok RW: Cerebrovascular P-glycoprotein expression is decreased in Creutzfeldt-Jakob disease. Acta Neuropathol 2006, 111: 436–443. 10.1007/s00401-006-0042-3PubMedCrossRef Vogelgesang S, Glatzel M, Walker LC, Kroemer HK, Aguzzi A, Warzok RW: Cerebrovascular P-glycoprotein expression is decreased in Creutzfeldt-Jakob disease. Acta Neuropathol 2006, 111: 436–443. 10.1007/s00401-006-0042-3PubMedCrossRef
8.
go back to reference Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de VR, de KO, van Oostrom JC, Portman A, Leenders KL: Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA. J Neural Transm 2008, 115: 1001–1009. 10.1007/s00702-008-0030-yPubMedCentralPubMedCrossRef Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de VR, de KO, van Oostrom JC, Portman A, Leenders KL: Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA. J Neural Transm 2008, 115: 1001–1009. 10.1007/s00702-008-0030-yPubMedCentralPubMedCrossRef
9.
go back to reference van Assema DM, Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD, Comans EF, Hoetjes NJ, Tolboom N, Langer O, Müller M, Scheltens P, Lammertsma AA, van Berckel BNM: Blood-brain barrier P-glycoprotein function in Alzheimer's disease. Brain 2011. doi: 10.1093/brain/awr298 van Assema DM, Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD, Comans EF, Hoetjes NJ, Tolboom N, Langer O, Müller M, Scheltens P, Lammertsma AA, van Berckel BNM: Blood-brain barrier P-glycoprotein function in Alzheimer's disease. Brain 2011. doi: 10.1093/brain/awr298
10.
go back to reference Langer O, Bauer M, Hammers A, Karch R, Pataraia E, Koepp MJ, Abrahim A, Luurtsema G, Brunner M, Sunder-Plassmann R, Zimprich F, Joukhadar C, Gentzsch S, Dudczak R, Kletter K, Müller M, Baumgartner C: Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[(11)C]verapamil. Epilepsia 2007, 48: 1774–1784. 10.1111/j.1528-1167.2007.01116.xPubMedCrossRef Langer O, Bauer M, Hammers A, Karch R, Pataraia E, Koepp MJ, Abrahim A, Luurtsema G, Brunner M, Sunder-Plassmann R, Zimprich F, Joukhadar C, Gentzsch S, Dudczak R, Kletter K, Müller M, Baumgartner C: Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[(11)C]verapamil. Epilepsia 2007, 48: 1774–1784. 10.1111/j.1528-1167.2007.01116.xPubMedCrossRef
11.
go back to reference Bartels AL, van Berckel BN, Lubberink M, Luurtsema G, Lammertsma AA, Leenders KL: Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease. Parkinsonism Relat Disord 2008, 14: 505–508. 10.1016/j.parkreldis.2007.11.007PubMedCrossRef Bartels AL, van Berckel BN, Lubberink M, Luurtsema G, Lammertsma AA, Leenders KL: Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease. Parkinsonism Relat Disord 2008, 14: 505–508. 10.1016/j.parkreldis.2007.11.007PubMedCrossRef
12.
go back to reference Bauer M, Karch R, Neumann F, Abrahim A, Wagner CC, Kletter K, Muller M, Zeitlinger M, Langer O: Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET. Eur J Clin Pharmacol 2009, 65: 941–946. 10.1007/s00228-009-0709-5PubMedCentralPubMedCrossRef Bauer M, Karch R, Neumann F, Abrahim A, Wagner CC, Kletter K, Muller M, Zeitlinger M, Langer O: Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET. Eur J Clin Pharmacol 2009, 65: 941–946. 10.1007/s00228-009-0709-5PubMedCentralPubMedCrossRef
13.
go back to reference Kreisl WC, Liow JS, Kimura N, Seneca N, Zoghbi SS, Morse CL, Herscovitch P, Pike VW, Innis RB: P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer 11C-N-desmethyl-loperamide. J Nucl Med 2010, 51: 559–566. 10.2967/jnumed.109.070151PubMedCentralPubMedCrossRef Kreisl WC, Liow JS, Kimura N, Seneca N, Zoghbi SS, Morse CL, Herscovitch P, Pike VW, Innis RB: P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer 11C-N-desmethyl-loperamide. J Nucl Med 2010, 51: 559–566. 10.2967/jnumed.109.070151PubMedCentralPubMedCrossRef
14.
go back to reference Seneca N, Zoghbi SS, Liow JS, Kreisl W, Herscovitch P, Jenko K, Gladding RL, Taku A, Pike VW, Innis RB: Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein. J Nucl Med 2009, 50: 807–813. 10.2967/jnumed.108.058453PubMedCentralPubMedCrossRef Seneca N, Zoghbi SS, Liow JS, Kreisl W, Herscovitch P, Jenko K, Gladding RL, Taku A, Pike VW, Innis RB: Human brain imaging and radiation dosimetry of 11C-N-desmethyl-loperamide, a PET radiotracer to measure the function of P-glycoprotein. J Nucl Med 2009, 50: 807–813. 10.2967/jnumed.108.058453PubMedCentralPubMedCrossRef
15.
go back to reference Kannan P, John C, Zoghbi SS, Halldin C, Gottesman MM, Innis RB, Hall MD: Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. Clin Pharmacol Ther 2009, 86: 368–377. 10.1038/clpt.2009.138PubMedCentralPubMedCrossRef Kannan P, John C, Zoghbi SS, Halldin C, Gottesman MM, Innis RB, Hall MD: Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications. Clin Pharmacol Ther 2009, 86: 368–377. 10.1038/clpt.2009.138PubMedCentralPubMedCrossRef
16.
go back to reference Syvanen S, Hammarlund-Udenaes M: Using PET studies of P-gp function to elucidate mechanisms underlying the disposition of drugs. Curr Top Med Chem 2010, 10: 1799–1809. 10.2174/156802610792927997PubMedCrossRef Syvanen S, Hammarlund-Udenaes M: Using PET studies of P-gp function to elucidate mechanisms underlying the disposition of drugs. Curr Top Med Chem 2010, 10: 1799–1809. 10.2174/156802610792927997PubMedCrossRef
17.
go back to reference Vogelgesang B, Echizen H, Schmidt E, Eichelbaum M: Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of l- and d-verapamil examined with a stable isotope technique. 1984. Br J Clin Pharmacol 2004, 58: S796-S803. 10.1111/j.1365-2125.2004.02299.xPubMedCentralPubMedCrossRef Vogelgesang B, Echizen H, Schmidt E, Eichelbaum M: Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of l- and d-verapamil examined with a stable isotope technique. 1984. Br J Clin Pharmacol 2004, 58: S796-S803. 10.1111/j.1365-2125.2004.02299.xPubMedCentralPubMedCrossRef
18.
go back to reference Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJ: Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography. Clin Pharmacol Ther 2006, 79: 540–548. 10.1016/j.clpt.2006.02.004PubMedCrossRef Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJ: Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography. Clin Pharmacol Ther 2006, 79: 540–548. 10.1016/j.clpt.2006.02.004PubMedCrossRef
19.
go back to reference Lubberink M, Luurtsema G, van Berckel BN, Boellaard R, Toornvliet R, Windhorst AD, Franssen EJ, Lammertsma AA: Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[11C]verapamil and PET. J Cereb Blood Flow Metab 2007, 27: 424–433. 10.1038/sj.jcbfm.9600349PubMedCrossRef Lubberink M, Luurtsema G, van Berckel BN, Boellaard R, Toornvliet R, Windhorst AD, Franssen EJ, Lammertsma AA: Evaluation of tracer kinetic models for quantification of P-glycoprotein function using (R)-[11C]verapamil and PET. J Cereb Blood Flow Metab 2007, 27: 424–433. 10.1038/sj.jcbfm.9600349PubMedCrossRef
20.
go back to reference Bartels AL, Kortekaas R, Bart J, Willemsen AT, de Klerk OL, de Vries JJ, van Oostrom JC, Leenders KL: Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: a possible role in progressive neurodegeneration. Neurobiol Aging 2009, 30: 1818–1824. 10.1016/j.neurobiolaging.2008.02.002PubMedCrossRef Bartels AL, Kortekaas R, Bart J, Willemsen AT, de Klerk OL, de Vries JJ, van Oostrom JC, Leenders KL: Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: a possible role in progressive neurodegeneration. Neurobiol Aging 2009, 30: 1818–1824. 10.1016/j.neurobiolaging.2008.02.002PubMedCrossRef
21.
go back to reference Wagner CC, Bauer M, Karch R, Feurstein T, Kopp S, Chiba P, Kletter K, Loscher W, Muller M, Zeitlinger M, Langer O: A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET. J Nucl Med 2009, 50: 1954–1961. 10.2967/jnumed.109.063289PubMedCentralPubMedCrossRef Wagner CC, Bauer M, Karch R, Feurstein T, Kopp S, Chiba P, Kletter K, Loscher W, Muller M, Zeitlinger M, Langer O: A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET. J Nucl Med 2009, 50: 1954–1961. 10.2967/jnumed.109.063289PubMedCentralPubMedCrossRef
22.
go back to reference Bauer M, Karch R, Neumann F, Wagner CC, Kletter K, Muller M, Loscher W, Zeitlinger M, Langer O: Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier. J Cereb Blood Flow Metab 2010, 30: 510–515. 10.1038/jcbfm.2009.265PubMedCentralPubMedCrossRef Bauer M, Karch R, Neumann F, Wagner CC, Kletter K, Muller M, Loscher W, Zeitlinger M, Langer O: Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier. J Cereb Blood Flow Metab 2010, 30: 510–515. 10.1038/jcbfm.2009.265PubMedCentralPubMedCrossRef
23.
go back to reference Muzi M, Mankoff DA, Link JM, Shoner S, Collier AC, Sasongko L, Unadkat JD: Imaging of cyclosporine inhibition of P-glycoprotein activity using 11C-verapamil in the brain: studies of healthy humans. J Nucl Med 2009, 50: 1267–1275. 10.2967/jnumed.108.059162PubMedCentralPubMedCrossRef Muzi M, Mankoff DA, Link JM, Shoner S, Collier AC, Sasongko L, Unadkat JD: Imaging of cyclosporine inhibition of P-glycoprotein activity using 11C-verapamil in the brain: studies of healthy humans. J Nucl Med 2009, 50: 1267–1275. 10.2967/jnumed.108.059162PubMedCentralPubMedCrossRef
24.
go back to reference Bart J, Groen HJ, Hendrikse NH, van der Graaf WT, Vaalburg W, de Vries EG: The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat Rev 2000, 26: 449–462. 10.1053/ctrv.2000.0194PubMedCrossRef Bart J, Groen HJ, Hendrikse NH, van der Graaf WT, Vaalburg W, de Vries EG: The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat Rev 2000, 26: 449–462. 10.1053/ctrv.2000.0194PubMedCrossRef
25.
go back to reference Didziapetris R, Japertas P, Avdeef A, Petrauskas A: Classification analysis of P-glycoprotein substrate specificity. J Drug Target 2003, 11: 391–406. 10.1080/10611860310001648248PubMedCrossRef Didziapetris R, Japertas P, Avdeef A, Petrauskas A: Classification analysis of P-glycoprotein substrate specificity. J Drug Target 2003, 11: 391–406. 10.1080/10611860310001648248PubMedCrossRef
26.
go back to reference Brix G, Zaers J, Adam LE, Bellemann ME, Ostertag H, Trojan H, Haberkorn U, Doll J, Oberdorfer F, Lorenz WJ: Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association. J Nucl Med 1997, 38: 1614–1623.PubMed Brix G, Zaers J, Adam LE, Bellemann ME, Ostertag H, Trojan H, Haberkorn U, Doll J, Oberdorfer F, Lorenz WJ: Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association. J Nucl Med 1997, 38: 1614–1623.PubMed
27.
go back to reference Luurtsema G, Windhorst AD, Mooijer MP, Herscheid JD, Lammertsma AA, Franssen EJ: Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. J Labelled Compds Radiopharm 2002, 45: 1199–1207. 10.1002/jlcr.632CrossRef Luurtsema G, Windhorst AD, Mooijer MP, Herscheid JD, Lammertsma AA, Franssen EJ: Fully automated high yield synthesis of (R)- and (S)-[C-11]verapamil for measuring P-glycoprotein function with positron emission tomography. J Labelled Compds Radiopharm 2002, 45: 1199–1207. 10.1002/jlcr.632CrossRef
28.
go back to reference Boellaard R, van LA, van Balen SC, Hoving BG, Lammertsma AA: Characteristics of a new fully programmable blood sampling device for monitoring blood radioactivity during PET. Eur J Nucl Med 2001, 28: 81–89. 10.1007/s002590000405PubMedCrossRef Boellaard R, van LA, van Balen SC, Hoving BG, Lammertsma AA: Characteristics of a new fully programmable blood sampling device for monitoring blood radioactivity during PET. Eur J Nucl Med 2001, 28: 81–89. 10.1007/s002590000405PubMedCrossRef
29.
go back to reference Luurtsema G, Molthoff CF, Schuit RC, Windhorst AD, Lammertsma AA, Franssen EJ: Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat. Nucl Med Biol 2005, 32: 87–93. 10.1016/j.nucmedbio.2004.06.007PubMedCrossRef Luurtsema G, Molthoff CF, Schuit RC, Windhorst AD, Lammertsma AA, Franssen EJ: Evaluation of (R)-[11C]verapamil as PET tracer of P-glycoprotein function in the blood-brain barrier: kinetics and metabolism in the rat. Nucl Med Biol 2005, 32: 87–93. 10.1016/j.nucmedbio.2004.06.007PubMedCrossRef
30.
go back to reference Mourik JE, Lubberink M, Klumpers UM, Comans EF, Lammertsma AA, Boellaard R: Partial volume corrected image derived input functions for dynamic PET brain studies: methodology and validation for [11C]flumazenil. Neuroimage 2008, 39: 1041–1050. 10.1016/j.neuroimage.2007.10.022PubMedCrossRef Mourik JE, Lubberink M, Klumpers UM, Comans EF, Lammertsma AA, Boellaard R: Partial volume corrected image derived input functions for dynamic PET brain studies: methodology and validation for [11C]flumazenil. Neuroimage 2008, 39: 1041–1050. 10.1016/j.neuroimage.2007.10.022PubMedCrossRef
31.
go back to reference Brix G, Doll J, Bellemann ME, Trojan H, Haberkorn U, Schmidlin P, Ostertag H: Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals. Eur J Nucl Med 1997, 24: 779–786.PubMed Brix G, Doll J, Bellemann ME, Trojan H, Haberkorn U, Schmidlin P, Ostertag H: Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals. Eur J Nucl Med 1997, 24: 779–786.PubMed
32.
go back to reference Mourik JE, Lubberink M, van Velden FH, Kloet RW, van Berckel BN, Lammertsma AA, Boellaard R: In vivo validation of reconstruction-based resolution recovery for human brain studies. J Cereb Blood Flow Metab 2010, 30: 381–389. 10.1038/jcbfm.2009.225PubMedCentralPubMedCrossRef Mourik JE, Lubberink M, van Velden FH, Kloet RW, van Berckel BN, Lammertsma AA, Boellaard R: In vivo validation of reconstruction-based resolution recovery for human brain studies. J Cereb Blood Flow Metab 2010, 30: 381–389. 10.1038/jcbfm.2009.225PubMedCentralPubMedCrossRef
33.
go back to reference Svarer C, Madsen K, Hasselbalch SG, Pinborg LH, Haugbol S, Frokjaer VG, Holm S, Paulson OB, Knudsen GM: MR-based automatic delineation of volumes of interest in human brain PET images using probability maps. Neuroimage 2005, 24: 969–979. 10.1016/j.neuroimage.2004.10.017PubMedCrossRef Svarer C, Madsen K, Hasselbalch SG, Pinborg LH, Haugbol S, Frokjaer VG, Holm S, Paulson OB, Knudsen GM: MR-based automatic delineation of volumes of interest in human brain PET images using probability maps. Neuroimage 2005, 24: 969–979. 10.1016/j.neuroimage.2004.10.017PubMedCrossRef
34.
go back to reference Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, Hume SP, Grasby PM, Lammertsma AA: Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET. Neuroimage 1998, 8: 426–440. 10.1006/nimg.1998.0379PubMedCrossRef Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, Hume SP, Grasby PM, Lammertsma AA: Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET. Neuroimage 1998, 8: 426–440. 10.1006/nimg.1998.0379PubMedCrossRef
35.
go back to reference Akaike H: A new look at the statistical model indentification. IEEE Trans Autom Contr 1974, 19: 716–723. 10.1109/TAC.1974.1100705CrossRef Akaike H: A new look at the statistical model indentification. IEEE Trans Autom Contr 1974, 19: 716–723. 10.1109/TAC.1974.1100705CrossRef
36.
go back to reference Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 1: 307–310.PubMedCrossRef Bland JM, Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986, 1: 307–310.PubMedCrossRef
Metadata
Title
Reproducibility of quantitative (R)-[11C]verapamil studies
Authors
Daniëlle ME van Assema
Mark Lubberink
Ronald Boellaard
Robert C Schuit
Albert D Windhorst
Philip Scheltens
Bart NM van Berckel
Adriaan A Lammertsma
Publication date
01-12-2012
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2012
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-2-1

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