DEVELOPING TARGETED HYBRID IMAGING PROBES BY CHELATOR SCAFFOLDING

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F17%3A73584147" target="_blank" >RIV/61989592:15110/17:73584147 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00182" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00182</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.bioconjchem.7b00182" target="_blank" >10.1021/acs.bioconjchem.7b00182</a>

Result language

angličtina

Original language name

DEVELOPING TARGETED HYBRID IMAGING PROBES BY CHELATOR SCAFFOLDING

Original language description

Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labelled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalisation and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumour xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumour uptake accompanied by slow blood clearance and retention in non-targeted tissues (spleen, liver and kidneys) leading to visualization of tumours at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine tune pharmacokinetics are needed to translate this into a clinical setting.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioconjugate Chemistry

ISSN

1043-1802

e-ISSN

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Volume of the periodical

28

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

1722-1733

UT code for WoS article

000404090500015

EID of the result in the Scopus database

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