Multimerization results in formation of re-bindable metabolites: A proof of concept study with FSC-based minigastrin imaging probes targeting CCK2R expression

PloS One
Dominik SummerClemens Decristoforo

Abstract

Positron emission tomography (PET) with radiolabelled peptide-based tracers has attracted great interest in oncology over the past decades. The success of imaging is closely related to sufficient uptake of the radiotracer in malignant tissue and for this sufficient biological half-life, particularly in the bloodstream, is mandatory. Fast enzymatic degradation during circulation leading to insufficient imaging abilities of peptide-based radioligands remains a major issue. The design of multimeric constructs, bearing multiple targeting moieties, has been widely applied to improve target interaction. This concept may also be applied to prolong the biological half-life of peptide-based radiopharmaceuticals as enzymatic degradation can result in formation of metabolites still capable to interact with the target binding site. In this study we aimed to identify such metabolites and therefore we utilized the siderophore-based bifunctional chelator fusarinine C (FSC) for the design of novel mono- and multimeric constructs, bearing minigastrin (MG) analogues as targeting moieties to address cholecystokinin-2 receptors (CCK2R) which are overexpressed in a variety of cancerous diseases and are well known for fast enzymatic degradation, par...Continue Reading

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Citations

Aug 6, 2020·Pharmaceuticals·Benedikt JudmannCarmen Wängler
Jan 14, 2021·Trends in Molecular Medicine·Verena I BöhmerPhilip H Elsinga
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marco VeronaMattia Asti
Jun 27, 2020·Current Medicinal Chemistry·Maximilian KlinglerElisabeth Von Guggenberg

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