Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects.
Purpose: [18F]MK6240 was developed for PET imaging of tau aggregates, which are implicated in Alzheimer's disease. The goal of this work was to evaluate the kinetics of [18F]MK6240 and to investigate different strategies for in-vivo quantification of tau aggregates in humans. Methods: Thirty-five su...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 46; no. 10; pp. 2099 - 2112 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Sep2019
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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=137794735&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137794735 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: Sep2019 vid: 46 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 137794735 10.1007/s00259-019-04419-z 137794735 ppf: 2099 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. aug: au: Guehl, Nicolas J. Wooten, Dustin W. Yokell, Daniel L. Moon, Sung-Hyun Dhaynaut, Maeva Katz, Samantha Moody, Kirsten A. Gharagouzloo, Codi Kas, Aurélie Johnson, Keith A. El Fakhri, Georges Normandin, Marc D. affil: Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA sug: ab: Purpose: [18F]MK6240 was developed for PET imaging of tau aggregates, which are implicated in Alzheimer's disease. The goal of this work was to evaluate the kinetics of [18F]MK6240 and to investigate different strategies for in-vivo quantification of tau aggregates in humans. Methods: Thirty-five subjects, consisting of 18 healthy controls (CTRL), 11 subjects with mild cognitive impairment (MCI) and six with Alzheimer's Disease (AD), underwent dynamic [18F]MK6240 PET scans. Arterial blood measurements were collected in 16 subjects (eight CTRLs, six MCIs and two AD) to measure whole blood and plasma concentration time courses. Radiometabolite analysis was performed on a subset of plasma samples. Various compartmental model configurations as well as the Logan and multilinear analysis (MA1) graphical methods with arterial plasma input function were tested. Simplified reference tissue methods were investigated, including Logan distribution volume ratio (DVR), multilinear reference tissue method (MRTM2), and static SUV ratio using the cerebellum as a reference region. Results: Whole blood:plasma ratio stabilized to 0.66 ± 0.01 after 15 min. Percent parent in plasma (%PP) followed a single exponential and ranged from 0 to 10% at 90 min. [18F]MK6240 in gray matter peaked quickly (SUV > 2 at ~3 min). The preferred compartmental model was a reversible two-tissue compartment model, with the blood contribution included as a model parameter (2T4k1v). Compartmental and graphical analysis methods with arterial input functions yielded concordant results, but rapid metabolism raised challenges for blood-based quantification. MCI and AD subjects demonstrated a broad range of VT as compared to CTRL subjects. DVR from MRTM2 and Logan reference tissue methods correlated with DVR calculated indirectly from compartmental modeling, but underestimation was observed in data sets with very high binding (DVR > 3). SUVR also underestimated indirect DVR from blood-based analyses in high binding regions, although a non-linear relationship was exhibited. Conclusions: [18F]MK6240 exhibited a wide dynamic range of uptake, with binding patterns in MCI/AD subjects consistent with neurofibrillary tau deposition patterns. Linearized reference tissue methods using an estimated average tissue-to-plasma efflux constant k ′ 2 ¯ and static SUVR agreed well with blood-based methods for most data sets; however, discrepancies were noted in the highest binding cases. Caution should therefore be exercised in application of simplified methods to such data sets, and in quantitative interpretation of corresponding outcomes. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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