PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [18F]PF-06684511.
Purpose: Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 47; no. 10; pp. 2429 - 2440 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Sep2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144890062&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144890062 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Sep2020 vid: 47 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 144890062 144076132 10.1007/s00259-020-04739-5 144890062 ppf: 2429 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: PET imaging of beta-secretase 1 in the human brain: radiation dosimetry, quantification, and test-retest examination of [18F]PF-06684511. aug: au: Arakawa, Ryosuke Takano, Akihiro Stenkrona, Per Stepanov, Vladimir Nag, Sangram Jahan, Mahabuba Grybäck, Per Bolin, Martin Chen, Laigao Zhang, Lei He, Ping Villalobos, Anabella McCarthy, Timothy J. Halldin, Christer Varrone, Andrea affil: Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden sug: ab: Purpose: Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [18F]PF-06684511 in healthy volunteers. Methods: Five subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (VT) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of VT were calculated as reliability measures. Results: In the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 μSv/MBq). The calculated ED was 24.7 ± 0.8 μSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. VT (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of VT (2TCM) were 16.5% (12.4–20.5%) and 0.496 (0.291–0.644). Conclusion: The ED of [18F]PF-06684511 was similar to other 18F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of VT was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [18F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain. Trial registration: EudraCT 2016-001110-19 (registered 2016-08-08) pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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