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Biophysics Reports 2016, 2(1): 1-20 https://doi.org/10.1007/s41048-016-0021-8
Review | Open Access | Issue | Published: 12 April 2016

Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging

Show Author's Information Jiyun Shi1,2,  Fan Wang1,2,  Shuang Liu3( )
Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Medical Isotopes Research Center, Peking University, Beijing 100191, China
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
Keywords:
Tumor imaging, Integrin αvβ3 , PET and SPECT radiotracers
Cite this article:
Shi J, Wang F, Liu S. Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging. Biophysics Reports, 2016, 2(1): 1-20. https://doi.org/10.1007/s41048-016-0021-8
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Abstract Full text About this article

The integrin family comprises 24 transmembrane receptors, each a heterodimeric combination of one of 18α and one of 8β subunits. Their main function is to integrate the cell adhesion and interaction with the extracellular microenvironment with the intracellular signaling and cytoskeletal rearrangement through transmitting signals across the cell membrane upon ligand binding. Integrin αvβ3 is a receptor for the extracellular matrix proteins containing arginine–glycine–aspartic (RGD) tripeptide sequence. The αvβ3 is generally expressed in low levels on the epithelial cells and mature endothelial cells, but it is highly expressed in many solid tumors. The αvβ3 levels correlate well with the potential for tumor metastasis and aggressiveness, which make it an important biological target for development of antiangiogenic drugs, and molecular imaging probes for early tumor diagnosis. Over the last decade, many radiolabeled cyclic RGD peptides have been evaluated as radiotracers for imaging tumors by SPECT or PET. Even though they are called “αvβ3-targeted” radiotracers, the radiolabeled cyclic RGD peptides are also able to bind αvβ5, α5β1, α6β4, α4β1, and αvβ6 integrins, which may help enhance their tumor uptake due to the “increased receptor population.” This article will use the multimeric cyclic RGD peptides as examples to illustrate basic principles for development of integrin-targeted radiotracers and focus on different approaches to maximize their tumor uptake and T/B ratios. It will also discuss important assays for pre-clinical evaluations of the integrin-targeted radiotracers, and their potential applications as molecular imaging tools for noninvasive monitoring of tumor metastasis and early detection of the tumor response to antiangiogenic therapy.


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About this article

Radiolabeled cyclic RGD peptides as radiotracers for tumor imaging

Show Author's information Jiyun Shi1,2, Fan Wang1,2, Shuang Liu3( )
Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Medical Isotopes Research Center, Peking University, Beijing 100191, China
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA

Abstract

The integrin family comprises 24 transmembrane receptors, each a heterodimeric combination of one of 18α and one of 8β subunits. Their main function is to integrate the cell adhesion and interaction with the extracellular microenvironment with the intracellular signaling and cytoskeletal rearrangement through transmitting signals across the cell membrane upon ligand binding. Integrin αvβ3 is a receptor for the extracellular matrix proteins containing arginine–glycine–aspartic (RGD) tripeptide sequence. The αvβ3 is generally expressed in low levels on the epithelial cells and mature endothelial cells, but it is highly expressed in many solid tumors. The αvβ3 levels correlate well with the potential for tumor metastasis and aggressiveness, which make it an important biological target for development of antiangiogenic drugs, and molecular imaging probes for early tumor diagnosis. Over the last decade, many radiolabeled cyclic RGD peptides have been evaluated as radiotracers for imaging tumors by SPECT or PET. Even though they are called “αvβ3-targeted” radiotracers, the radiolabeled cyclic RGD peptides are also able to bind αvβ5, α5β1, α6β4, α4β1, and αvβ6 integrins, which may help enhance their tumor uptake due to the “increased receptor population.” This article will use the multimeric cyclic RGD peptides as examples to illustrate basic principles for development of integrin-targeted radiotracers and focus on different approaches to maximize their tumor uptake and T/B ratios. It will also discuss important assays for pre-clinical evaluations of the integrin-targeted radiotracers, and their potential applications as molecular imaging tools for noninvasive monitoring of tumor metastasis and early detection of the tumor response to antiangiogenic therapy.

Keywords: Tumor imaging, Integrin αvβ3 , PET and SPECT radiotracers

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Publication history

Received: 05 November 2015
Accepted: 01 March 2016
Published: 12 April 2016
Issue date: February 2016

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© The Author(s) 2016

Acknowledgements

This work was supported, in part, by Purdue University and R21 EB017237-01 (S. L.) from the National Institute of Biomedical Imaging and Bioengineering (NIBIB).

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