title: Optimized Quantification of Translocator Protein Radioligand ¹⁸F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers.
abstract: Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the (18)F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling.
  
  
  METHODS
  Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent (18)F-DPA-714 PET with arterial and venous sampling. (18)F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1- and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V(T)) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples.
  
  
  RESULTS
  The distribution pattern of (18)F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of (18)F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation < 5%). For each region of interest, V(T) was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V(T) calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation.
  
  
  CONCLUSIONS
  Genotyping of subjects is a prerequisite for a reliable quantification of (18)F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate (18)F-DPA-714 V(T) in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.
authors.affiliation: CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France sonia.lavisse@cea.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lavisse
authors.affiliation: Institut du Cerveau et de la Moelle épinière, Inserm-U1127 and Sorbonne University, UPMC-UMRS-1127, Paris, France CNRS-UMR7225, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Lorenzo
authors.affiliation: CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Peyronneau
authors.affiliation: Institut du Cerveau et de la Moelle épinière, Inserm-U1127 and Sorbonne University, UPMC-UMRS-1127, Paris, France CNRS-UMR7225, Paris, France CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France Department of Neuroimaging, Institute of Psychiatry, King's College London, London, England.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France Neurology Department, Centre Expert Parkinson, CHU Henri Mondor, AP-HP, Créteil, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Thiriez
authors.affiliation: CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Kuhnast
authors.affiliation: CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Comtat
authors.affiliation: CEA-DSV-I2BM, MIRCen, Fontenay-aux-Roses, France CNRS-UMR9199, Universités Paris-Sud and Paris-Saclay, Fontenay-aux-Roses, France Neurology Department, Centre Expert Parkinson, CHU Henri Mondor, AP-HP, Créteil, France Paris-Est University, Créteil, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Remy
authors.affiliation: Institut du Cerveau et de la Moelle épinière, Inserm-U1127 and Sorbonne University, UPMC-UMRS-1127, Paris, France CNRS-UMR7225, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.affiliation: CEA-DSV-I2BM, SHFJ and IMIV, UMR1023 Inserm/CEA/Paris-Sud University, Orsay, France CEA-DSV-I2BM, Neurospin, Gif-sur-Yvette, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bottlaender
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D002531:Cerebellum / Q000000981:diagnostic imaging; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000473:pathology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D018079:Receptors, GABA / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging
chemical_list: D005462:Fluorine Radioisotopes; D008024:Ligands; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: 18F-DPA-714; PET; TSPO; genotyped human; quantification