title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark ling.feng@nru.dk.
authors.forename: Ling
authors.initials: L
authors.lastname: Feng
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gerda
authors.initials: G
authors.lastname: Thomsen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: de Nijs
authors.affiliation: Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibeke A
authors.initials: VA
authors.lastname: Larsen
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Jensen
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Dea
authors.initials: D
authors.lastname: Adamsen
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Dyssegaard
authors.affiliation: Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Walter
authors.initials: W
authors.lastname: Fischer
authors.affiliation: Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Meden
authors.affiliation: Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Derk
authors.initials: D
authors.lastname: Krieger
authors.affiliation: Department of Neuroanaesthesiology and Centre of Inflammation and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Epilepsy Clinic, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Pinborg
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D001932:Brain Neoplasms / Q000000981:diagnostic imaging; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics*; D005260:Female; D005838:Genotype; D005909:Glioblastoma / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055815:Young Adult
chemical_list: C504993:6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo(1,2-a)pyridine-3-acetamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: 123I-CLINDE SPECT; TSPO binding; neurologic patients; quantification