Development of Purine-Derived <sup>18</sup>F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

Galante, Eva; Okamura, Toshimitsu; Sander, Kerstin; Kikuchi, Tatsuya; Okada, Maki; Zhang, Ming‐Rong; Robson, Mathew; Badar, Adam; Lythgoe, Mark F.; Koepp, Matthias J.; Årstad, Erik

doi:10.1021/jm401764a

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…choroid plexus, glia cells or brain capillary endothelial cells) has not yet been fully established. Galante and colleagues recently synthesized a 18 Flabeled version of this MRP1 tracer (Galante et al, 2014) for which brain clearance was also shown to be dependent on mMRP1 function.…”

Section: Brain Transportersmentioning

confidence: 99%

Imaging techniques to study drug transporter function in vivo

Tournier

Stieger

Langer

2018

Pharmacology & Therapeutics

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Transporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imaging allows pharmacokinetic parameters in different tissues and organs to be obtained in a non-invasive or minimally invasive way. The aim of this overview is to summarize the current status in the field of molecular imaging of drug transporters. The overview is focused on human studies, both for the characterization of transport systems for imaging agents as well as for the determination of drug pharmacokinetics, and makes reference to animal studies where necessary. We conclude that despite certain methodological limitations, imaging has a great potential to study transporters at work in humans and that imaging will become an important tool, not only in drug development but also in medicine. Imaging allows the mechanistic aspects of transport proteins to be studied, as well as elucidating the influence of genetic background, pathophysiological states and drug-drug interactions on the function of transporters involved in the disposition of drugs.

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Section: Brain Transportersmentioning

confidence: 99%

Imaging techniques to study drug transporter function in vivo

Tournier

Stieger

Langer

2018

Pharmacology & Therapeutics

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“…Numerous N-alkylations with [ 18 F]FETos have been performed (Scheme 22). 49,57,[82][83][84][85][86][87][88][89][90][91][92][93][94][95] General reaction conditions involve the use of polar aprotic solvents such as DMSO, DMF or MeCN and temperatures ranging from 82 to 130 1C. Mostly, inorganic bases with a range of different pK a -values were employed depending on the reactivity of the corresponding amine reactant.…”

Section: [ 18 F]fluoroethyl Halides and Sulfonatesmentioning

confidence: 99%

Fluorine-18 labelled building blocks for PET tracer synthesis

et al. 2017

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Positron emission tomography (PET) is an important driver for present day healthcare. Fluorine-18 is the most widely used radioisotope for PET imaging and a thorough overview of the available radiochemistry methodology is a prerequisite for selection of a synthetic approach for new fluorine-18 labelled PET tracers. These PET tracers can be synthesised either by late-stage radiofluorination, introducing fluorine-18 in the last step of the synthesis, or by a building block approach (also called modular build-up approach), introducing fluorine-18 in a fast and efficient manner in a building block, which is reacted further in one or multiple reaction steps to form the PET tracer. This review presents a comprehensive overview of the synthesis and application of fluorine-18 labelled building blocks since 2010.

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“…However, it is not certain if this innovative approach to measure ABCC1 function can be translated to human subjects, as no clinical application of this PET tracer has been reported yet. Very recently, a fluorine-18-labelled version of this ABCC1 probe has been reported by another research group (Galante et al, 2014). Of course, the most accurate approach for estimating the risk for developing AD would be the direct measurement of Aβ clearance from the AD brain.…”

Section: Abc Transporters – An Outlookmentioning

confidence: 99%

Alzheimer’s and ABC transporters — new opportunities for diagnostics and treatment

Pahnke

Langer

Krohn

2014

Neurobiology of Disease

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Much has been said about the increasing number of demented patients and the main risk factor ‘age’. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain’s barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias.

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Development of Purine-Derived ¹⁸F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

Cited by 15 publications

References 32 publications

Imaging techniques to study drug transporter function in vivo

Imaging techniques to study drug transporter function in vivo

Fluorine-18 labelled building blocks for PET tracer synthesis

Alzheimer’s and ABC transporters — new opportunities for diagnostics and treatment

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Development of Purine-Derived 18F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET

Cited by 15 publications

References 32 publications

Imaging techniques to study drug transporter function in vivo

Imaging techniques to study drug transporter function in vivo

Fluorine-18 labelled building blocks for PET tracer synthesis

Alzheimer’s and ABC transporters — new opportunities for diagnostics and treatment

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Product

Resources

About

Development of Purine-Derived ¹⁸F-Labeled Pro-drug Tracers for Imaging of MRP1 Activity with PET