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

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 - 2014/12/1

Y1 - 2014/12/1

N2 - This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4′-123I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide (123I-CLINDE) in neurologic patients. 123I-CLINDE is structurally related to well-known PET ligands such as 18F-PBR111 and 18F-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 123I-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, 123I-CLINDE binding parameters were not significantly changed. Thus, 123I-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, 123ICLINDE 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 123I-CLINDE binding with SPECT.

AB - This study provides the first comprehensive quantification of translocator protein (TSPO) binding using SPECT and 6-chloro-2-(4′-123I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide (123I-CLINDE) in neurologic patients. 123I-CLINDE is structurally related to well-known PET ligands such as 18F-PBR111 and 18F-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 123I-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, 123I-CLINDE binding parameters were not significantly changed. Thus, 123I-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, 123ICLINDE 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 123I-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

SN - 0161-5505

VL - 55

SP - 1966

EP - 1972

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

IS - 12

ER -