In Vivo Quantification of Cerebral Translocator Protein Binding in Humans Using 6-Chloro-2-(4′-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide SPECT
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In Vivo Quantification of Cerebral Translocator Protein Binding in Humans Using 6-Chloro-2-(4′-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide SPECT. / Feng, Ling; Svarer, Claus; Thomsen, Gerda; de Nijs, Robin; Larsen, Vibeke A; Jensen, Per; Adamsen, Dea; Dyssegaard, Agnete; Fischer, Walter; Meden, Per; Krieger, Derk; Møller, Kirsten; Knudsen, Gitte M; Pinborg, Lars H.
I: Journal of Nuclear Medicine, Bind 55, Nr. 12, 12.2014, s. 1966-1972.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - In Vivo Quantification of Cerebral Translocator Protein Binding in Humans Using 6-Chloro-2-(4′-123I-Iodophenyl)-3-(N,N-Diethyl)-Imidazo[1,2-a]Pyridine-3-Acetamide SPECT
AU - Feng, Ling
AU - Svarer, Claus
AU - Thomsen, Gerda
AU - de Nijs, Robin
AU - Larsen, Vibeke A
AU - Jensen, Per
AU - Adamsen, Dea
AU - Dyssegaard, Agnete
AU - Fischer, Walter
AU - Meden, Per
AU - Krieger, Derk
AU - Møller, Kirsten
AU - Knudsen, Gitte M
AU - Pinborg, Lars H
N1 - © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2014/12
Y1 - 2014/12
N2 - UNLABELLED: This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide ((123)I-CLINDE) in neurologic patients. (123)I-CLINDE is structurally related to well-known PET ligands such as (18)F-PBR111 and (18)F-DPA-714.METHODS: Six patients with cerebral stroke and 4 patients with glioblastoma multiforme (GBM) underwent 150-min dynamic SPECT scans with arterial blood sampling. Four of the patients were rescanned. All patients were genotyped for the rs6971 polymorphism. Volumes of interest were delineated on the individual SPECT scans and the coregistered MR images. Compartmental and graphical models using arterial input or the cerebellum as a reference region were used to quantify (123)I-CLINDE binding.RESULTS: Among the 6 models investigated, the 2-tissue-compartment model with arterial input described the time-activity data best. Time-stability analyses suggested that acquisition time should be at least 90 min. Intersubject variation in the cerebellar distribution volume (VT) was clearly related to the TSPO genotype. In the stroke patients the VT in the periinfarction zone, compared with VT in the ipsilateral cerebellum, ranged from 1.4 to 3.4, and in the GBM patients the VT in the tumor, compared with the VT in the cerebellum, ranged from 1.8 to 3.4. In areas of gadolinium extravasation, (123)I-CLINDE binding parameters were not significantly changed. Thus, (123)I-CLINDE binding does not appear to be importantly affected by blood-brain barrier disruption.CONCLUSION: As demonstrated within a group of stroke and GBM patients, (123)I-CLINDE SPECT can be used for quantitative assessment of TSPO expression in vivo. Because of the absence of a region devoid of TSPO, reference tissue models should be used with caution. The 2-tissue-compartment kinetic analysis of a 90-min dynamic scan with arterial blood sampling is recommended for the quantification of (123)I-CLINDE binding with SPECT.
AB - UNLABELLED: This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4'-(123)I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide ((123)I-CLINDE) in neurologic patients. (123)I-CLINDE is structurally related to well-known PET ligands such as (18)F-PBR111 and (18)F-DPA-714.METHODS: Six patients with cerebral stroke and 4 patients with glioblastoma multiforme (GBM) underwent 150-min dynamic SPECT scans with arterial blood sampling. Four of the patients were rescanned. All patients were genotyped for the rs6971 polymorphism. Volumes of interest were delineated on the individual SPECT scans and the coregistered MR images. Compartmental and graphical models using arterial input or the cerebellum as a reference region were used to quantify (123)I-CLINDE binding.RESULTS: Among the 6 models investigated, the 2-tissue-compartment model with arterial input described the time-activity data best. Time-stability analyses suggested that acquisition time should be at least 90 min. Intersubject variation in the cerebellar distribution volume (VT) was clearly related to the TSPO genotype. In the stroke patients the VT in the periinfarction zone, compared with VT in the ipsilateral cerebellum, ranged from 1.4 to 3.4, and in the GBM patients the VT in the tumor, compared with the VT in the cerebellum, ranged from 1.8 to 3.4. In areas of gadolinium extravasation, (123)I-CLINDE binding parameters were not significantly changed. Thus, (123)I-CLINDE binding does not appear to be importantly affected by blood-brain barrier disruption.CONCLUSION: As demonstrated within a group of stroke and GBM patients, (123)I-CLINDE SPECT can be used for quantitative assessment of TSPO expression in vivo. Because of the absence of a region devoid of TSPO, reference tissue models should be used with caution. The 2-tissue-compartment kinetic analysis of a 90-min dynamic scan with arterial blood sampling is recommended for the quantification of (123)I-CLINDE binding with SPECT.
KW - Adult
KW - Aged
KW - Bicyclo Compounds, Heterocyclic
KW - Brain
KW - Brain Neoplasms
KW - Female
KW - Genotype
KW - Glioblastoma
KW - Humans
KW - Image Processing, Computer-Assisted
KW - Magnetic Resonance Imaging
KW - Male
KW - Middle Aged
KW - Radiopharmaceuticals
KW - Receptors, GABA
KW - Stroke
KW - Tomography, Emission-Computed, Single-Photon
KW - Young Adult
U2 - 10.2967/jnumed.114.143727
DO - 10.2967/jnumed.114.143727
M3 - Journal article
C2 - 25453044
VL - 55
SP - 1966
EP - 1972
JO - The Journal of Nuclear Medicine
JF - The Journal of Nuclear Medicine
SN - 0161-5505
IS - 12
ER -
ID: 137326412