Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD

Haubner, Roland; Weber, Wolfgang A.; Beer, Ambros J.; Vabuliene, Eugenija; Reim, Daniel; Sarbia, Mario; Becker, Karl-Friedrich; Goebel, Michael C.; Hein, Rüdiger; Wester, Hans-Jürgen; Kessler, Horst; Schwaiger, Markus

doi:10.1371/journal.pmed.0020070

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Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [ ¹⁸F]Galacto-RGD

research-article

Author(s): Roland Haubner ¹ ^, ^¤a ^, ^* , Wolfgang A Weber ¹ ^, ^¤b , Ambros J Beer ¹ ^, ² , Eugenija Vabuliene ¹ , Daniel Reim ¹ , Mario Sarbia ³ , Karl-Friedrich Becker ³ , Michael Goebel ⁴ , Rüdiger Hein ⁵ , Hans-Jürgen Wester ¹ , Horst Kessler ⁶ , Markus Schwaiger ¹

Editor(s): Peter Ell

Publication date (Electronic): 29 March 2005

Journal: PLoS Medicine

Publisher: Public Library of Science

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Abstract

Background

The integrin αvβ3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of αvβ3 expression. We developed [ ¹⁸F]Galacto-RGD, a ¹⁸F-labeled glycosylated αvβ3 antagonist, allowing monitoring of αvβ3 expression with positron emission tomography (PET).

Methods and Findings

Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [ ¹⁸F]Galacto-RGD in the tumor correlates with αvβ3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize αvβ3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [ ¹⁸F]Galacto-RGD with PET enables noninvasive quantitative assessment of the αvβ3 expression pattern on tumor and endothelial cells in patients with malignant tumors.

Conclusions

Molecular imaging with [ ¹⁸F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the αvβ3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.

Abstract

Visualising integrins with PET scanning can show angiogenesis in tumors and also be used to monitor anti-angiogenic therapy

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Most cited references 50

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The alpha(V)beta(3) integrin receptor plays an important role in human tumor metastasis and tumor-induced angiogenesis. The in vivo inhibition of this receptor by antibodies or by cyclic peptides containing the RGD sequence may in the future be used to selectively suppress these diseases. Here we investigate the influence of N-methylation of the active and selective alpha(V)beta(3) antagonist cyclo(RGDfV) (L1) on biological activity. Cyclo(RGDf-N(Me)V-) (P5) was found to be even more active than L1 and is one of the most active and selective compounds in inhibiting vitronectin binding to the alpha(V)beta(3) integrin. Its high-resolution, three-dimensional structure in water was determined by NMR techniques, distance geometry calculations, and molecular dynamics calculations, providing more insight into the structure-activity relationship.

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Author and article information

Contributors

: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS Med

Journal ID (publisher-id): pmed

Title: PLoS Medicine

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Print): 1549-1277

ISSN (Electronic): 1549-1676

Publication date (Print): March 2005

Publication date (Electronic): 29 March 2005

Volume: 2

Issue: 3

Electronic Location Identifier: e70

Affiliations

[1] 1Nuklearmedizinische Klinik und Poliklinik Technische Universität MünchenGermany

[2] 2Institut für Röntgendiagnostik Technische Universität MünchenGermany

[3] 3Institut für Pathologie Technische Universität MünchenGermany

[4] 4Klinik für Orthopädie und Sportorthopädie Technische Universität MünchenGermany

[5] 5Klinik und Poliklinik für Dermatologie und Allergologie, Technische Universität MünchenGermany

[6] 6Department Chemie, Lehrstuhl II für Organische Chemie Technische Universität München, GarchingGermany

Institute of Nuclear Medicine United Kingdom

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Author Contributions: R. Haubner, W.A. Weber, H.J. Wester, H. Kessler, and M. Schwaiger conceived and designed the experiments. R. Haubner, A.J. Beer, E. Vabuliene, D. Reim, K.F. Becker, M. Goebel, and R. Hein performed the experiments. R. Haubner, W.A. Weber, M. Sarbia and A.J. Beer analyzed the data. R. Haubner, W.A. Weber, A.J. Beer, H.J. Wester and M. Schwaiger contributed to the writing of the paper.

* To whom correspondence should be addressed. E-mail: Roland.Haubner@ 123456uibk.ac.at

¤a Current address: Universitätsklinik für Nuklearmedizin, Medizinische Universität Innsbruck, Austria

¤b Current address: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America

Article

DOI: 10.1371/journal.pmed.0020070

PMC ID: 1069665

PubMed ID: 15783258

SO-VID: 83c5a6f1-3c7d-4719-ac9f-173103a9d745

Copyright © Copyright: © 2005 Haubner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

History

Date received : 4 October 2004

Date accepted : 28 January 2005

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