Challenges and Perspectives of the Hybridization of PET with Functional MRI or Ultrasound for Neuroimaging

Tournier, Nicolas; Comtat, Claude; Lebon, Vincent; Gennisson, Jean‐Luc

doi:10.1016/j.neuroscience.2020.10.015

Cited by 18 publications

(8 citation statements)

References 121 publications

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“…To the best of our knowledge, it is the first application of PET-MR DWB imaging for the study of dynamic processes such as PK and DDIs in humans. Compared with current static or whole-body acquisition routinely performed using PET-CT (computed tomography) scanners, DWB imaging PET-MR reduces volunteer exposure to radiation, allows for repeated scanning without additional CT for attenuation correction, and ensures accurate delineation in organs including soft tissues [53]. This original method enables quantification of radiolabeled substrates of transporters in several organs in a parallel manner which in turn allows for direct comparison of the importance of transporter function between organs in each individual.…”

Section: Discussionmentioning

confidence: 99%

[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body

Marie

Breuil

Chalampalakis

et al. 2022

Biomedicine & Pharmacotherapy

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Section: Discussionmentioning

confidence: 99%

[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body

Marie

Breuil

Chalampalakis

et al. 2022

Biomedicine & Pharmacotherapy

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“…In radiotracer development, co-injection of radiotracers with pharmacological doses of corresponding unlabeled compounds is only used to investigate the specific binding to brain regions [57]. We assume this strategy will gain interest for multimodal pharmacological imaging protocols on simultaneous hybrid PET-MR systems [58]. Using CNS-active dose, the time-course of PET-derived target engagement can therefore be directly compared with the hemodynamic response assessed using pharmacological MRI (phMRI) or other pharmacodynamic parameters in the same individual [59].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo

Auvity

Goutal

Caillé

et al. 2021

Neuropsychopharmacol.

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A wide range of buprenorphine doses are used for either pain management or maintenance therapy in opioid addiction. The complex in vitro profile of buprenorphine, with affinity for µ-, δ-and κ-opioid receptors (OR), makes it difficult to predict its dose-related neuropharmacology in vivo. In rats, microPET imaging and pretreatment by OR antagonists were performed to assess the binding of radiolabeled buprenorphine (microdose 11 Cbuprenorphine) to OR subtypes in vivo (n=4 per condition). The µ-selective antagonist naloxonazine (10 mg/kg) and the non-selective OR-antagonist naloxone (1 mg/kg) blocked the binding of 11 C-buprenorphine while pretreatment by the δ-selective (naltrindole, 3 mg/kg) or the κ-selective antagonist (norbinaltorphimine, 10 mg/kg) did not. In four macaques, PET imaging and kinetic modeling enabled description of the regional brain kinetics of 11 Cbuprenorphine, co-injected with increasing doses of unlabeled buprenorphine. No saturation of the brain penetration of buprenorphine was observed for doses up to 0.11 mg/kg. Regional differences in buprenorphine-associated receptor occupancy were observed. Analgesic doses of buprenorphine (0.003 and 0.006 mg/kg) respectively occupied 20% and 49% of receptors in the thalamus while saturating the low but significant binding observed in cerebellum and occipital cortex. Occupancy >90% was achieved in most brain regions with plasma concentrations >7 µg/L. PET data obtained after co-injection of an analgesic dose of buprenorphine (0.003 mg/kg) predicted the binding potential of microdose 11 Cbuprenorphine. This strategy could be further combined with pharmacodynamic exploration or pharmacological MRI to investigate the neuropharmacokinetics and neuroreceptor correlate, at least at µ-OR, of the acute effects of buprenorphine in humans.

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“…In the absence of such reference region, increase in BBB permeability can be quantified by comparing [ 18 F]FDS V T or AUC brain /AUC blood obtained in a control (sham) group or in the same animals before any intervention, following a longitudinal design. This illustrates the added value of absolute quantitative PET compared with other neuroimaging techniques for noninvasive determination of different levels of BBB permeation in various situations [26].…”

Section: Discussionmentioning

confidence: 85%

“…Brain SPECT using [ 99m Tc]DTPA (MW = 487) is also widely used as a BBB integrity marker [25]. The predominant use of MRI and SPECT to investigate BBB integrity is likely due to the wide availability of corresponding imaging probes [26]. In humans, the clinical proof-of-concept of FUS-induced BBB disruption has been achieved using DCE-MRI to assess and localize BBB disruption in vivo [12].…”

Section: Introductionmentioning

confidence: 99%

[18F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound

et al. 2021

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Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood–brain barrier (BBB) permeability in vivo. Positron-emission tomography (PET) imaging using [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) was evaluated as a small-molecule (paracellular) marker of blood–brain barrier (BBB) integrity. [18F]FDS was straightforwardly produced from chemical reduction of commercial [18F]2-deoxy-2-fluoro-D-glucose. [18F]FDS and the invasive BBB integrity marker Evan’s blue (EB) were i.v. injected in mice after an optimized FUS protocol designed to generate controlled hemispheric BBB disruption. Quantitative determination of the impact of FUS on the BBB permeability was determined using kinetic modeling. A 2.2 ± 0.5-fold higher PET signal (n = 5; p < 0.01) was obtained in the sonicated hemisphere and colocalized with EB staining observed post mortem. FUS significantly increased the blood-to-brain distribution of [18F]FDS by 2.4 ± 0.8-fold (VT; p < 0.01). Low variability (=10.1%) of VT values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [18F]FDS PET provides a readily available, sensitive and reproducible marker of BBB permeability to noninvasively monitor the extent of BBB disruption induced by FUS in vivo.

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Challenges and Perspectives of the Hybridization of PET with Functional MRI or Ultrasound for Neuroimaging

Cited by 18 publications

References 121 publications

[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body

[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body

Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo

[18F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound

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