Therapeutic Radiopharmaceuticals Targeting Integrin αvβ6

ACS Omega
Stefanie Felicitas FärberJohannes Notni

Abstract

The epithelial integrin αvβ6 is expressed by many malignant carcinoma cell types, including pancreatic cancer, and thus represents a promising target for radionuclide therapy. The peptide cyclo(FRGDLAFp(NMe)K) was decorated with different chelators (DOTPI, DOTAGA, and DOTA). The Lu(III) complexes of these conjugates exhibited comparable αvβ6 integrin affinities (IC50 ranging from 0.3 to 0.8 nM) and good selectivities against other integrins (IC50 for αvβ8 >43 nM; for α5β1 >238 nM; and for αvβ3, αvβ5, and αIIbβ3 >1000 nM). Although different formal charges of the Lu(III) chelates (ranging from 0 to 4) resulted in strongly varying degrees of hydrophilicity (log D ranging from -3.0 to -4.1), biodistributions in murine H2009 xenografts of the Lu-177-labeled compounds (except the DOTPI derivative) were quite similar and comparable to our previously reported αvβ6 integrin positron emission tomography tracer Ga-68-avebehexin. Hence, combinations of existing Ga-68- and Lu-177-labeled c(FRGDLAFp(NMe)K) derivatives could be utilized for αvβ6 integrin-targeted theranostics, whereas our data nonetheless suggest that further improvement of pharmacokinetics might be necessary to ensure clinical success.

References

Nov 27, 1992·Journal of Medicinal Chemistry·G D HartmanG Zhang
Apr 22, 1994·Science·P C BrooksD A Cheresh
Jan 16, 1999·The Journal of Biological Chemistry·S KraftS L Goodman
May 24, 2008·Nature Reviews. Cancer·Christie J AvraamidesJudith A Varner
Jul 16, 2009·Current Drug Targets·A Bandyopadhyay, S Raghavan
Jan 29, 2011·Anti-cancer Agents in Medicinal Chemistry·Carlos Mas-MorunoHorst Kessler
May 6, 2011·Theranostics·Gang Niu, Xiaoyuan Chen
Dec 8, 2011·Chemistry : a European Journal·Johannes NotniHans-Jürgen Wester
Oct 10, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Jakub SimečekJohannes Notni
Apr 25, 2013·Chemistry : a European Journal·Jakub ŠimečekJohannes Notni
Sep 21, 2013·Expert Opinion on Therapeutic Patents·Tobias G KappHorst Kessler
Oct 30, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Alison E JohnJohn F Marshall
Feb 15, 2014·Molecular Pharmaceutics·Xiaohua ZhuZhen Cheng
Apr 9, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Zhaofei LiuFan Wang
May 23, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Zsolt BaranyaiJohannes Notni
Nov 9, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zequn LiWeibo Niu
Jun 23, 2016·Chemistry : a European Journal·Johannes Notni, Hans-Jürgen Wester
Dec 17, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Johannes NotniHans-Jürgen Wester
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jun 8, 2017·Cancers·Hanadi Talal AhmedahHelen M Sheldrake
Jun 22, 2017·Cancer Letters·Jun Niu, Zequn Li
Aug 24, 2017·Chemistry : a European Journal·Alexander WurzerJohannes Notni
Sep 5, 2017·Cancers·Markus NieberlerHorst Kessler

❮ Previous
Next ❯

Citations

Nov 8, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sven H HausnerJulie L Sutcliffe
Jun 11, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Neil Gerard QuigleyJohannes Notni
Jul 17, 2018·Molecular Pharmaceutics·Alexander WurzerJohannes Notni
Sep 25, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Neil Gerard QuigleyJohannes Notni
Nov 4, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Ryusuke NakamotoSanjiv Sam Gambhir

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
enzyme-linked immunosorbent assay
xenograft
size-exclusion chromatography

Software Mentioned

OriginPro
Siemens Inveon Research Workspace

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Johannes NotniHans-Jürgen Wester
Current Pharmaceutical Design
Mikhail A RubtsovGjumrakch Aliev
© 2022 Meta ULC. All rights reserved