Catriona Wimberley1, Sonia Lavisse2, Vincent Brulon3, Marie-Anne Peyronneau3, Claire Leroy3, Benedetta Bodini4, Philippe Remy2,5, Bruno Stankoff4, Irène Buvat3, Michel Bottlaender3,6. 1. IMIV, Inserm, CEA, Université Paris-Sud, Université Paris Saclay, Orsay, France catriona.wimberley@cea.fr. 2. MIRCen, CEA and CNRS-UMR9199, Université Paris-Sud, Fontenay-aux-Roses, France. 3. IMIV, Inserm, CEA, Université Paris-Sud, Université Paris Saclay, Orsay, France. 4. Institut du Cerveau et de la Moelle épinière, Inserm, U 1127, F-75013, Paris, France, and Sorbonne University, UPMC Université Paris 06, UMR S 1127, Paris, France. 5. Neurology Department, Centre Expert Parkinson, and NeurATRIS, CHU Henri Mondor, AP-HP and Université Paris-Est Créteil, France; and. 6. Neurospin, CEA, Gif-sur-Yvette, France.
Abstract
18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.
18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.
Authors: Marloes H J Hagens; Sandeep V Golla; Martijn T Wijburg; Maqsood Yaqub; Dennis Heijtel; Martijn D Steenwijk; Patrick Schober; John J P Brevé; Robert C Schuit; Tristan A Reekie; Michael Kassiou; Anne-Marie van Dam; Albert D Windhorst; Joep Killestein; Frederik Barkhof; Bart N M van Berckel; Adriaan A Lammertsma Journal: J Neuroinflammation Date: 2018-11-13 Impact factor: 8.322
Authors: Erik Nutma; Jodie A Stephenson; Rianne P Gorter; Joy de Bruin; Deirdre M Boucherie; Cornelius K Donat; Marjolein Breur; Paul van der Valk; Paul M Matthews; David R Owen; Sandra Amor Journal: Brain Date: 2019-11-01 Impact factor: 13.501