Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific hsp70 peptide-based probe

Stangl S, Varga J, Freysoldt B, Trajkovic-Arsic M, Siveke JT, Greten FR, Ntziachristos V, Multhoff G (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Cancer Research American Association for Cancer Research

Book Volume: 74

Pages Range: 6903-6912

Journal Issue: 23

DOI: 10.1158/0008-5472.CAN-14-0413

Abstract

Although in vivo targeting of tumors using fl uorescently labeled probes has greatly gained in importance over the last few years, most of the clinically applied reagents lack tumor cell speci fi city. Our novel tumor cell- penetrating peptide-based probe (TPP) recognizes an epitope of Hsp70 that is exclusively present on the cell surface of a broad variety of human and mouse tumors and metastases, but not on normal tissues. Because of the rapid turnover rate of membrane Hsp70, fl uorescently labeled TPP is continuously internalized into syngeneic, spontaneous, chemically/genetically induced and xenograft tumors following intravenous administration, thereby enabling site-specific labeling of primary tumors and metastases. In contrast with the commercially available nonpeptide small molecule avb3 - integrin antagonist IntegriSense, TPP exhibits a signi fi cantly higher tumor-to-background contrast and stronger tumor-specific signal intensity in all tested tumor models. Moreover, in contrast with IntegriSense, TPP reliably differentiates between tumor cells and cells of the tumor microenvironment, such as tumor-associated macrophages and fibroblasts, which were found to be membrane-Hsp70 negative. Therefore, TPP provides a useful tool for multimodal imaging of tumors and metastases that might help to improve our understanding of tumorigenesis and allow the establishment of improved diagnostic procedures and more accurate therapeutic monitoring. TPP might also be a promising platform for tumor-speci fic drug delivery and other Hsp70-based targeted therapies. Cancer Res 74(23); 6903-12.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Institut für Tumorbiologie und experimentelle Therapie / Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Stangl, S., Varga, J., Freysoldt, B., Trajkovic-Arsic, M., Siveke, J.T., Greten, F.R.,... Multhoff, G. (2014). Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific hsp70 peptide-based probe. Cancer Research, 74(23), 6903-6912. https://dx.doi.org/10.1158/0008-5472.CAN-14-0413

MLA:

Stangl, Stefan, et al. "Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific hsp70 peptide-based probe." Cancer Research 74.23 (2014): 6903-6912.

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