Evaluation of [<sup>18</sup>F]-<i>N</i>-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies

Kramer, Vasko; Brooks, Allen F.; Haeger, Arlette; Kuljiš, Rodrigo O.; Rafique, Waqas; Koeppe, Robert A.; Raffel, David M.; Frey, Kirk A.; Amaral, Horacio; Scott, Peter J. H.; Riss, Patrick J.

doi:10.1021/acschemneuro.9b00639

Cited by 22 publications

(26 citation statements)

References 36 publications

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“…In this case, these agents will never reach their intended subcellular target(s). Such promiscuous or selective substrates would be of great use as AD diagnostics [e.g., positron emission tomography (PET) tracers] to track ABC transporter function at the BBB itself [60] (e.g., ABCB1 [61,62] or ABCC1 [63,64]). However, for future drug design of AD therapeutics to affect ABC transporters participating in (subcellular) vesicle membrane formation and composition, these compounds should rather not be substrates but allosteric modulators.…”

Section: Vesicular Abc Transporters: Implications For Pharmacokineticsmentioning

confidence: 99%

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Stefan

Leck

Namasivayam

et al. 2020

Future Drug. Discov.

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Section: Vesicular Abc Transporters: Implications For Pharmacokineticsmentioning

confidence: 99%

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Stefan

Leck

Namasivayam

et al. 2020

Future Drug. Discov.

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“…This (Riss and Aigbirhio 2011). This radiochemistry underwent various improvements (Kramer et al 2020). In 2020, Riss and Scott implemented this protocol for the synthesis [ 18 F]N-methyl lansoprazole ([ 18 F]NML) (4.6% RCY and A m = 120.1 GBq/μmol), a candidate for Alzheimer's Tau imaging (Frost et al 2019).…”

Section: Radiosynthesis Of [ 18 F]trifluoromethyl-containing Moleculesmentioning

confidence: 99%

Closing the gap between 19F and 18F chemistry

Ajenjo

Destro

Cornelissen

et al. 2021

EJNMMI radiopharm. chem.

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Positron emission tomography (PET) has become an invaluable tool for drug discovery and diagnosis. The positron-emitting radionuclide fluorine-18 is frequently used in PET radiopharmaceuticals due to its advantageous characteristics; hence, methods streamlining access to 18F-labelled radiotracers can make a direct impact in medicine. For many years, access to 18F-labelled radiotracers was limited by the paucity of methodologies available, and the poor diversity of precursors amenable to 18F-incorporation. During the last two decades, 18F-radiochemistry has progressed at a fast pace with the appearance of numerous methodologies for late-stage 18F-incorporation onto complex molecules from a range of readily available precursors including those that do not require pre-functionalisation. Key to these advances is the inclusion of new activation modes to facilitate 18F-incorporation. Specifically, new advances in late-stage 19F-fluorination under transition metal catalysis, photoredox catalysis, and organocatalysis combined with the availability of novel 18F-labelled fluorination reagents have enabled the invention of novel processes for 18F-incorporation onto complex (bio)molecules. This review describes these major breakthroughs with a focus on methodologies for C–18F bond formation. This reinvigorated interest in 18F-radiochemistry that we have witnessed in recent years has made a direct impact on 19F-chemistry with many laboratories refocusing their efforts on the development of methods using nucleophilic fluoride instead of fluorination reagents derived from molecular fluorine gas.

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“…Moreover, the authors found that the ratio of [ 18 F]difluoromethylidene increased, and the radiochemical yield of [ 18 F]LNS was not higher than 7%. Kramer et al described the synthesis of fluorine-18-labelled N-methyl lanosoprazole ([ 18 F]NML), an analogue of lansoprazole (Scheme 4) [45]. They followed the procedure reported by Fawaz et al involving nucleophilic addition of n.c.a.…”

Section: Aliphatic [ 18 F]cf 3 Compoundsmentioning

confidence: 99%

Advances in [18F]Trifluoromethylation Chemistry for PET Imaging

Francis

Wuest

2021

Molecules

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Positron emission tomography (PET) is a preclinical and clinical imaging technique extensively used to study and visualize biological and physiological processes in vivo. Fluorine-18 (18F) is the most frequently used positron emitter for PET imaging due to its convenient 109.8 min half-life, high yield production on small biomedical cyclotrons, and well-established radiofluorination chemistry. The presence of fluorine atoms in many drugs opens new possibilities for developing radioligands labelled with fluorine-18. The trifluoromethyl group (CF3) represents a versatile structural motif in medicinal and pharmaceutical chemistry to design and synthesize drug molecules with favourable pharmacological properties. This fact also makes CF3 groups an exciting synthesis target from a PET tracer discovery perspective. Early attempts to synthesize [18F]CF3-containing radiotracers were mainly hampered by low radiochemical yields and additional challenges such as low radiochemical purity and molar activity. However, recent innovations in [18F]trifluoromethylation chemistry have significantly expanded the chemical toolbox to synthesize fluorine-18-labelled radiotracers. This review presents the development of significant [18F]trifluoromethylation chemistry strategies to apply [18F]CF3-containing radiotracers in preclinical and clinical PET imaging studies. The continuous growth of PET as a crucial functional imaging technique in biomedical and clinical research and the increasing number of CF3-containing drugs will be the primary drivers for developing novel [18F]trifluoromethylation chemistry strategies in the future.

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Evaluation of [¹⁸F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies

Cited by 22 publications

References 36 publications

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Closing the gap between 19F and 18F chemistry

Advances in [18F]Trifluoromethylation Chemistry for PET Imaging

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Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies

Cited by 22 publications

References 36 publications

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Vesicular ATP-binding cassette transporters in human disease: relevant aspects of their organization for future drug development

Closing the gap between 19F and 18F chemistry

Advances in [18F]Trifluoromethylation Chemistry for PET Imaging

Contact Info

Product

Resources

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Evaluation of [¹⁸F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies