Synthesis, 18F-labelling and radiopharmacological characterisation of the C-terminal 30mer of Clostridium perfringens enterotoxin as a potential claudin-targeting peptide

Löser, Reik; Bader, Miriam; Kuchar, Manuela; Wodtke, Robert; Lenk, Jens; Wodtke, Johanna; Kuhne, Konstantin; Bergmann, Ralf; Haase-Kohn, Cathleen; Urbanová, Marie; Steinbach, Jörg; Pietzsch, Jens

doi:10.1007/s00726-018-2657-9

Cited by 4 publications

(1 citation statement)

References 79 publications

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“…Hence, we expected to synthesise both 18 F-AS69 and 18 F-AS69-ApoE with high molar activity comparable to that of [ 18 F]FET (454 ± 144 GBq/μmol, immediately following 30 min of synthesis). This molar activity was remarkably higher than that from other methods of protein fluorine-18 labelling using N-succinimidyl 4-[ 18 F]fluorobenzoate or aluminium 18 F-fluoride-1,4,7-triazanonane-1,4,7-triacetate conjugate (typically 1-100 GBq/mol) [33][34][35][36] . This advantage allows for more sensitive target detection and high-contrast images.…”

Section: Discussionmentioning

confidence: 74%

Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

Morito

Harada

Iwata

et al. 2021

Sci Rep

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Brain positron emission tomography (PET) imaging with radiolabelled proteins is an emerging concept that potentially enables visualization of unique molecular targets in the brain. However, the pharmacokinetics and protein radiolabelling methods remain challenging. Here, we report the performance of an engineered, blood–brain barrier (BBB)-permeable affibody molecule that exhibits rapid clearance from the brain, which was radiolabelled using a unique fluorine-18 labelling method, a cell-free protein radiosynthesis (CFPRS) system. AS69, a small (14 kDa) dimeric affibody molecule that binds to the monomeric and oligomeric states of α-synuclein, was newly designed for brain delivery with an apolipoprotein E (ApoE)-derived brain shuttle peptide as AS69-ApoE (22 kDa). The radiolabelled products 18F-AS69 and 18F-AS69-ApoE were successfully synthesised using the CFPRS system. Notably, 18F-AS69-ApoE showed higher BBB permeability than 18F-AS69 in an ex vivo study at 10 and 30 min post injection and was partially cleared from the brain at 120 min post injection. These results suggest that small, a brain shuttle peptide-fused fluorine-18 labelled protein binders can potentially be utilised for brain molecular imaging.

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Section: Discussionmentioning

confidence: 74%

Synthesis and pharmacokinetic characterisation of a fluorine-18 labelled brain shuttle peptide fusion dimeric affibody

Morito

Harada

Iwata

et al. 2021

Sci Rep

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Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging

et al. 2023

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The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases. These insights have considerably stimulated drug discovery efforts towards lysyl oxidases as targets over the last decade. This review article summarises the biochemical and structural properties of theses enzymes. Their involvement in tumour progression and metastasis is highlighted from a biochemical point of view, taking into consideration both the extracellular and intracellular action of lysyl oxidases. More recently reported inhibitor compounds are discussed with an emphasis on their discovery, structure‐activity relationships and the results of their biological characterisation. Molecular probes developed for imaging of lysyl oxidase activity are reviewed from the perspective of their detection principles, performance and biomedical applications.

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