Ling Feng1, Claus Svarer2, Gerda Thomsen2, Robin de Nijs3, Vibeke A Larsen4, Per Jensen2, Dea Adamsen2, Agnete Dyssegaard2, Walter Fischer5, Per Meden6, Derk Krieger6, Kirsten Møller7, Gitte M Knudsen2, Lars H Pinborg8. 1. Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark ling.feng@nru.dk. 2. Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 3. Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 4. Department of Radiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 5. Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 6. Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen, Denmark. 7. Department of Neuroanaesthesiology and Centre of Inflammation and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and. 8. Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Epilepsy Clinic, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract
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.
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 neurologicpatients. (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 strokepatients 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.
Authors: Cornelius K Donat; Khaled Gaber; Jürgen Meixensberger; Peter Brust; Lars H Pinborg; Henrik H Hansen; Jens D Mikkelsen Journal: Neuromolecular Med Date: 2016-03-11 Impact factor: 3.843
Authors: Bastian Zinnhardt; Maximilian Wiesmann; Lisa Honold; Cristina Barca; Michael Schäfers; Amanda J Kiliaan; Andreas H Jacobs Journal: Theranostics Date: 2018-04-03 Impact factor: 11.556