Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies

Maqsood Yaqub; Ronald Boellaard; Bart N M van Berckel; Nelleke Tolboom; Gert Luurtsema; Anke A Dijkstra; Mark Lubberink; Albert D Windhorst; Philip Scheltens; Adriaan A Lammertsma

doi:10.1007/s11307-009-0208-1

Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies

Maqsood Yaqub^*, Ronald Boellaard, Bart N M van Berckel, Nelleke Tolboom, Gert Luurtsema, Anke A Dijkstra, Mark Lubberink, Albert D Windhorst, Philip Scheltens, Adriaan A Lammertsma

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

PURPOSE: Different pharmacokinetic methods for [18F]FDDNP studies were evaluated using both simulations and clinical data.

PROCEDURES: Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP(ND), was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios).

RESULTS: For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP(ND) using 2T1M correlated better with SRTM then direct BP(ND). Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP(ND) obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain.

CONCLUSIONS: SRTM is the method of choice for quantitative analysis of [18F]FDDNP even if it is unclear whether labeled metabolites enter the brain.

Original language	English
Pages (from-to)	322-333
Number of pages	12
Journal	Molecular Imaging and Biology
Volume	11
Issue number	5
DOIs	https://doi.org/10.1007/s11307-009-0208-1
Publication status	Published - 2009
Externally published	Yes

Keywords

Aged
Alzheimer Disease/diagnostic imaging
Brain/diagnostic imaging
Brain Chemistry
Computer Simulation
Fluorine Radioisotopes/pharmacokinetics
Humans
Magnetic Resonance Imaging
Middle Aged
Models, Biological
Nitriles/pharmacokinetics
Positron-Emission Tomography/methods
Radiopharmaceuticals/pharmacokinetics
Reference Values

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10.1007/s11307-009-0208-1

Cite this

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title = "Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies",

abstract = "PURPOSE: Different pharmacokinetic methods for [18F]FDDNP studies were evaluated using both simulations and clinical data.PROCEDURES: Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP(ND), was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios).RESULTS: For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP(ND) using 2T1M correlated better with SRTM then direct BP(ND). Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP(ND) obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain.CONCLUSIONS: SRTM is the method of choice for quantitative analysis of [18F]FDDNP even if it is unclear whether labeled metabolites enter the brain.",

keywords = "Aged, Alzheimer Disease/diagnostic imaging, Brain/diagnostic imaging, Brain Chemistry, Computer Simulation, Fluorine Radioisotopes/pharmacokinetics, Humans, Magnetic Resonance Imaging, Middle Aged, Models, Biological, Nitriles/pharmacokinetics, Positron-Emission Tomography/methods, Radiopharmaceuticals/pharmacokinetics, Reference Values",

author = "Maqsood Yaqub and Ronald Boellaard and {van Berckel}, {Bart N M} and Nelleke Tolboom and Gert Luurtsema and Dijkstra, {Anke A} and Mark Lubberink and Windhorst, {Albert D} and Philip Scheltens and Lammertsma, {Adriaan A}",

year = "2009",

doi = "10.1007/s11307-009-0208-1",

language = "English",

volume = "11",

pages = "322--333",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "5",

}

TY - JOUR

T1 - Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies

AU - Yaqub, Maqsood

AU - Boellaard, Ronald

AU - van Berckel, Bart N M

AU - Tolboom, Nelleke

AU - Luurtsema, Gert

AU - Dijkstra, Anke A

AU - Lubberink, Mark

AU - Windhorst, Albert D

AU - Scheltens, Philip

AU - Lammertsma, Adriaan A

PY - 2009

Y1 - 2009

N2 - PURPOSE: Different pharmacokinetic methods for [18F]FDDNP studies were evaluated using both simulations and clinical data.PROCEDURES: Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP(ND), was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios).RESULTS: For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP(ND) using 2T1M correlated better with SRTM then direct BP(ND). Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP(ND) obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain.CONCLUSIONS: SRTM is the method of choice for quantitative analysis of [18F]FDDNP even if it is unclear whether labeled metabolites enter the brain.

AB - PURPOSE: Different pharmacokinetic methods for [18F]FDDNP studies were evaluated using both simulations and clinical data.PROCEDURES: Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP(ND), was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios).RESULTS: For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP(ND) using 2T1M correlated better with SRTM then direct BP(ND). Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP(ND) obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain.CONCLUSIONS: SRTM is the method of choice for quantitative analysis of [18F]FDDNP even if it is unclear whether labeled metabolites enter the brain.

KW - Aged

KW - Alzheimer Disease/diagnostic imaging

KW - Brain/diagnostic imaging

KW - Brain Chemistry

KW - Computer Simulation

KW - Fluorine Radioisotopes/pharmacokinetics

KW - Humans

KW - Magnetic Resonance Imaging

KW - Middle Aged

KW - Models, Biological

KW - Nitriles/pharmacokinetics

KW - Positron-Emission Tomography/methods

KW - Radiopharmaceuticals/pharmacokinetics

KW - Reference Values

U2 - 10.1007/s11307-009-0208-1

DO - 10.1007/s11307-009-0208-1

M3 - Article

C2 - 19340487

SN - 1536-1632

VL - 11

SP - 322

EP - 333

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 5

ER -

Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies

Abstract

Keywords

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