6 research outputs found
sj-pdf-1-jcb-10.1177_0271678X231205661 - Supplemental material for [<sup>18</sup>F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging
No full textSupplemental material, sj-pdf-1-jcb-10.1177_0271678X231205661 for [18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging by Agne Knyzeliene, Mark G MacAskill, Carlos J Alcaide-Corral, Timaeus EF Morgan, Martyn C Henry, Christophe Lucatelli, Sally L Pimlott, Andrew Sutherland and Adriana AS Tavares in Journal of Cerebral Blood Flow & Metabolism</p
[18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging
No full textNeuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism (∼15–20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]LW223 has the required properties to become a successful TSPO PET radiotracer
Sexually dimorphic murine brain uptake of the 18 kDa translocator protein PET radiotracer [18F]LW223
No full textThe 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. PET with
18 kDa translocator protein radiotracers [11C]PBR28 in humans and [18F]GE180 in mice has demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [18F]LW223 exhibited sexually dimorphic uptake in healthy murine brain and peripheral organs. Male and female C57Bl6/J mice (13.6 ± 5.4 weeks, 26.8 ± 5.4 g, mean ± SD) underwent 2 h PET scanning post-administration of [18F]LW223 (6.7 ± 3.6 MBq). Volume of interest and parametric analyses were performed using standard uptake values (90–120 min). Statistical differences were assessed by unpaired t-test or two-way ANOVA with Šidak’s test (alpha = 0.05). The uptake of [18F]LW223 was significantly higher across multiple regions of the male mouse brain, with the most pronounced difference detected in hypothalamus (P < 0.0001). Males also exhibited significantly higher [18F]LW223 uptake in the heart when compared to females (P = 0.0107). Data support previous findings on sexually dimorphic 18 kDa translocator protein radiotracer uptake patterns in mice and highlight the need to conduct sex-controlled comparisons in 18 kDa translocator protein PET imaging studies.File descriptions are included in a Readme.txt file
[18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging
No full textNeuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology.
Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the
18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PETradiotracer,
[18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the
use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]
LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging
with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods,
standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low
VND in the brain (<10% of total binding) and low radiometabolism ( 15–20%). The 2-tissue compartment model
provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F]
LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]
LW223 has the required properties to become a successful TSPO PET radiotracer.File descriptions are included in a Readme.txt fil
Sexually dimorphic murine brain uptake of the 18 kDa translocator protein PET radiotracer [18F]LW223
No full textThe 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. PET with 18 kDa translocator protein radiotracers [11C]PBR28 in humans and [18F]GE180 in mice has demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [18F]LW223 exhibited sexually dimorphic uptake in healthy murine brain and peripheral organs. Male and female C57Bl6/J mice (13.6 ± 5.4 weeks, 26.8 ± 5.4 g, mean ± SD) underwent 2 h PET scanning post-administration of [18F]LW223 (6.7 ± 3.6 MBq). Volume of interest and parametric analyses were performed using standard uptake values (90–120 min). Statistical differences were assessed by unpaired t-test or two-way ANOVA with Šidak’s test (alpha = 0.05). The uptake of [18F]LW223 was significantly higher across multiple regions of the male mouse brain, with the most pronounced difference detected in hypothalamus (P < 0.0001). Males also exhibited significantly higher [18F]LW223 uptake in the heart when compared to females (P = 0.0107). Data support previous findings on sexually dimorphic 18 kDa translocator protein radiotracer uptake patterns in mice and highlight the need to conduct sex-controlled comparisons in 18 kDa translocator protein PET imaging studies
[18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging
No full textNeuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PETradiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F] LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism ( 15–20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F] LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F] LW223 has the required properties to become a successful TSPO PET radiotracer
