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...
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Nature Portfolio
2021
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oai:doaj.org-article:956ae6697f2b4d23a1f6acaf3aaf905f2021-12-02T15:07:47ZMinimally invasive quantification of cerebral P2X7R occupancy using dynamic [18F]JNJ-64413739 PET and MRA-driven image derived input function10.1038/s41598-021-95715-y2045-2322https://doaj.org/article/956ae6697f2b4d23a1f6acaf3aaf905f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95715-yhttps://doaj.org/toc/2045-2322Abstract [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.Nathalie MertensMark E. SchmidtAnja HijzenDonatienne Van WeehaeghePaulien RavenstijnMarleen DepreJan de HoonKoen Van LaereMichel KooleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q 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 |
| 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. |
| format |
article |
| author |
Nathalie Mertens Mark E. Schmidt Anja Hijzen Donatienne Van Weehaeghe Paulien Ravenstijn Marleen Depre Jan de Hoon Koen Van Laere Michel Koole |
| 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 Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/956ae6697f2b4d23a1f6acaf3aaf905f |
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