DEVELOPING TARGETED HYBRID IMAGING PROBES BY CHELATOR SCAFFOLDING

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

DEVELOPING TARGETED HYBRID IMAGING PROBES BY CHELATOR SCAFFOLDING

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

DEVELOPING TARGETED HYBRID IMAGING PROBES BY CHELATOR SCAFFOLDING

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Bioconjugate Chemistry

ISSN

1043-1802

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1722-1733

Kód UT WoS článku

000404090500015

EID výsledku v databázi Scopus

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