Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function
Abstract [18F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minim...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2021-08-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-95715-y |
id |
doaj-956ae6697f2b4d23a1f6acaf3aaf905f |
---|---|
record_format |
Article |
spelling |
doaj-956ae6697f2b4d23a1f6acaf3aaf905f2021-08-15T11:27:23ZengNature Publishing GroupScientific Reports2045-23222021-08-0111111110.1038/s41598-021-95715-yMinimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input functionNathalie Mertens0Mark E. Schmidt1Anja Hijzen2Donatienne Van Weehaeghe3Paulien Ravenstijn4Marleen Depre5Jan de Hoon6Koen Van Laere7Michel Koole8Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU LeuvenJanssen Research and DevelopmentJanssen Research and DevelopmentNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU LeuvenJanssen Research and DevelopmentCenter for Clinical Pharmacology, University Hospital and KU LeuvenCenter for Clinical Pharmacology, University Hospital and KU LeuvenNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU LeuvenNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital and KU LeuvenAbstract [18F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (VT) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose VT,IDIF values were compared with corresponding VT,AIF estimates using a arterial input function (AIF), in terms of absolute values, test–retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose VT,IDIF values and corresponding receptor occupancies showed only limited bias (Bland–Altman analysis: 0.06 ± 0.27 and 3.1% ± 6.4%) while demonstrating a high correlation (Spearman ρ = 0.78 and ρ = 0.98 respectively). In terms of test–retest reliability, regional intraclass correlation coefficients were 0.98 ± 0.02 for VT,IDIF compared to 0.97 ± 0.01 for VT,AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [18F]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility.https://doi.org/10.1038/s41598-021-95715-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathalie Mertens Mark E. Schmidt Anja Hijzen Donatienne Van Weehaeghe Paulien Ravenstijn Marleen Depre Jan de Hoon Koen Van Laere Michel Koole |
spellingShingle |
Nathalie Mertens Mark E. Schmidt Anja Hijzen Donatienne Van Weehaeghe Paulien Ravenstijn Marleen Depre Jan de Hoon Koen Van Laere Michel Koole Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function Scientific Reports |
author_facet |
Nathalie Mertens Mark E. Schmidt Anja Hijzen Donatienne Van Weehaeghe Paulien Ravenstijn Marleen Depre Jan de Hoon Koen Van Laere Michel Koole |
author_sort |
Nathalie Mertens |
title |
Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function |
title_short |
Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function |
title_full |
Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function |
title_fullStr |
Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function |
title_full_unstemmed |
Minimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function |
title_sort |
minimally invasive quantification of cerebral p2x7r occupancy using dynamic [18f]jnj-64413739 pet and mra-driven image derived input function |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-08-01 |
description |
Abstract [18F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (VT) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose VT,IDIF values were compared with corresponding VT,AIF estimates using a arterial input function (AIF), in terms of absolute values, test–retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose VT,IDIF values and corresponding receptor occupancies showed only limited bias (Bland–Altman analysis: 0.06 ± 0.27 and 3.1% ± 6.4%) while demonstrating a high correlation (Spearman ρ = 0.78 and ρ = 0.98 respectively). In terms of test–retest reliability, regional intraclass correlation coefficients were 0.98 ± 0.02 for VT,IDIF compared to 0.97 ± 0.01 for VT,AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [18F]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility. |
url |
https://doi.org/10.1038/s41598-021-95715-y |
work_keys_str_mv |
AT nathaliemertens minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT markeschmidt minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT anjahijzen minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT donatiennevanweehaeghe minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT paulienravenstijn minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT marleendepre minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT jandehoon minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT koenvanlaere minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction AT michelkoole minimallyinvasivequantificationofcerebralp2x7roccupancyusingdynamic18fjnj64413739petandmradrivenimagederivedinputfunction |
_version_ |
1721206761617096704 |