Preparation and Characterization of an Engineered FGF1 Conjugated to 161Tb for Targeting of FGFRs

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F26722445%3A_____%2F25%3AN0000085" target="_blank" >RIV/26722445:_____/25:N0000085 - isvavai.cz</a>

Alternative codes found

RIV/68407700:21340/25:00381207

Result on the web

<a href="https://pubs.acs.org/doi/pdf/10.1021/acsomega.4c09179" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/acsomega.4c09179</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsomega.4c09179" target="_blank" >10.1021/acsomega.4c09179</a>

Result language

angličtina

Original language name

Preparation and Characterization of an Engineered FGF1 Conjugated to 161Tb for Targeting of FGFRs

Original language description

The fibroblast growth factor receptor family members, FGFR1-4, are frequently overexpressed in various solid tumors, including breast cancer and sarcomas. This overexpression highlights the potential of the family of FGFRs as promising targets for cancer therapy. However, conventional FGFR kinase inhibitors often encounter challenges such as limited efficacy or drug resistance. In this study, we pursue an alternative strategy by designing a conjugate of the FGFR ligand FGF1 with the radioisotope 161Tb, for targeted therapy in FGFR-overexpressing cancer cells. FGF1 was engineered (eFGF1) to incorporate a single cysteine at the C terminus for site-specific labeling with a DOTA chelator. eFGF1-DOTA was mixed with the radioisotope 161Tb under mild conditions, resulting in a labeling efficiency above 90%. The nonradioactive ligands were characterized by mass spectrometry, while radioligands were characterized by thin-layer chromatography. The targeting function of the radioligands was assessed through confocal microscopy, flow cytometry, and Western blot analysis, focusing on binding to cancer cells and the activation of downstream signaling pathways related to FGFR. When compared to MCF-7 and RD cell lines with low FGFR expression, eFGF1-DOTA-Tb[161Tb] radioligands demonstrated significantly higher accumulation in FGFR-overexpressing cell lines (MCF-7 FGFR1 and RMS559), leading to enhanced cytotoxicity. Besides radionuclides, eFGF1 can also deliver doxorubicin (DOX) into cancer cells. Considering these characteristics, eFGF1-DOTA-Tb[161Tb] and eFGF1-DOX emerge as promising candidates for FGFR-targeted cancer therapy, and further evaluation in vivo is warranted.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

—

OECD FORD branch

10609 - Biochemical research methods

Project

<a href="/en/project/TO01000074" target="_blank" >TO01000074: Efficient Low-energy Electron Cancer Therapy with Terbium-161</a><br>

Continuities

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

Publication year

2025

Confidentiality

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

Name of the periodical

ACS Omega

ISSN

2470-1343

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

5730 - 5743

UT code for WoS article

—

EID of the result in the Scopus database

2-s2.0-85216964747