Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites

Gert Luurtsema; Robert C Schuit; Kevin Takkenkamp; Mark Lubberink; N Harry Hendrikse; Albert D Windhorst; Carla F M Molthoff; Nelleke Tolboom; Bart N M van Berckel; Adriaan A Lammertsma

doi:10.1016/j.nucmedbio.2008.09.002

Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites

Gert Luurtsema^*
, Robert C Schuit
, Kevin Takkenkamp
, Mark Lubberink
, N Harry Hendrikse
, Albert D Windhorst
, Carla F M Molthoff
, Nelleke Tolboom
, Bart N M van Berckel
, Adriaan A Lammertsma

^*Corresponding author for this work

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

Abstract

[(18)F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [(18)F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [(18)F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar (18)F-labelled fragments, probably formed from N-dealkylation of [(18)F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake.

Original language	English
Pages (from-to)	869-74
Number of pages	6
Journal	Nuclear medicine and biology
Volume	35
Issue number	8
DOIs	https://doi.org/10.1016/j.nucmedbio.2008.09.002
Publication status	Published - Nov 2008
Externally published	Yes

Keywords

Alzheimer Disease/diagnostic imaging
Animals
Blood-Brain Barrier
Brain/metabolism
Chromatography, High Pressure Liquid
Fluorine Radioisotopes
Humans
Nitriles/metabolism
Positron-Emission Tomography
Radiopharmaceuticals/metabolism
Rats
Rats, Wistar

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10.1016/j.nucmedbio.2008.09.002

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@article{3c43f3983f9d4a33afe7bf697011473a,

title = "Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites",

abstract = "[(18)F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [(18)F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [(18)F]FDDNP. After 10 min, more than 80\% of plasma radioactivity was identified as polar (18)F-labelled fragments, probably formed from N-dealkylation of [(18)F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake.",

keywords = "Alzheimer Disease/diagnostic imaging, Animals, Blood-Brain Barrier, Brain/metabolism, Chromatography, High Pressure Liquid, Fluorine Radioisotopes, Humans, Nitriles/metabolism, Positron-Emission Tomography, Radiopharmaceuticals/metabolism, Rats, Rats, Wistar",

author = "Gert Luurtsema and Schuit, \{Robert C\} and Kevin Takkenkamp and Mark Lubberink and Hendrikse, \{N Harry\} and Windhorst, \{Albert D\} and Molthoff, \{Carla F M\} and Nelleke Tolboom and \{van Berckel\}, \{Bart N M\} and Lammertsma, \{Adriaan A\}",

year = "2008",

month = nov,

doi = "10.1016/j.nucmedbio.2008.09.002",

language = "English",

volume = "35",

pages = "869--74",

journal = "Nuclear medicine and biology",

issn = "0969-8051",

publisher = "Elsevier",

number = "8",

}

TY - JOUR

T1 - Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites

AU - Luurtsema, Gert

AU - Schuit, Robert C

AU - Takkenkamp, Kevin

AU - Lubberink, Mark

AU - Hendrikse, N Harry

AU - Windhorst, Albert D

AU - Molthoff, Carla F M

AU - Tolboom, Nelleke

AU - van Berckel, Bart N M

AU - Lammertsma, Adriaan A

PY - 2008/11

Y1 - 2008/11

N2 - [(18)F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [(18)F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [(18)F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar (18)F-labelled fragments, probably formed from N-dealkylation of [(18)F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake.

AB - [(18)F]FDDNP is a positron emission tomography (PET) tracer for determining amyloid plaques and neurofibrillary tangles in the brain in vivo. In order to quantify binding of this tracer properly, a metabolite-corrected plasma input function is required. The purpose of the present study was to develop a sensitive method for measuring [(18)F]FDDNP and its radiolabelled metabolites in plasma. The second aim was to assess whether these radiolabelled metabolites enter the brain. In humans, there was extensive metabolism of [(18)F]FDDNP. After 10 min, more than 80% of plasma radioactivity was identified as polar (18)F-labelled fragments, probably formed from N-dealkylation of [(18)F]FDDNP. These labelled metabolites were reproduced in vitro using human hepatocytes. PET studies in rats showed that these polar metabolites can penetrate the blood-brain barrier and result in uniform brain uptake.

KW - Alzheimer Disease/diagnostic imaging

KW - Animals

KW - Blood-Brain Barrier

KW - Brain/metabolism

KW - Chromatography, High Pressure Liquid

KW - Fluorine Radioisotopes

KW - Humans

KW - Nitriles/metabolism

KW - Positron-Emission Tomography

KW - Radiopharmaceuticals/metabolism

KW - Rats

KW - Rats, Wistar

U2 - 10.1016/j.nucmedbio.2008.09.002

DO - 10.1016/j.nucmedbio.2008.09.002

M3 - Article

C2 - 19026948

SN - 0969-8051

VL - 35

SP - 869

EP - 874

JO - Nuclear medicine and biology

JF - Nuclear medicine and biology

IS - 8

ER -

Peripheral metabolism of [(18)F]FDDNP and cerebral uptake of its labelled metabolites

Abstract

Keywords

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