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Stangl, S.* ; Varga, J.* ; Freysoldt, B.* ; Trajkovic-Arsic, M.* ; Siveke, J.T.* ; Greten, F.R.* ; Ntziachristos, V. ; Multhoff, G.

Selective in vivo imaging of tumors with a tumor cell-specific Hsp70 peptide-based probe.

Cancer Res. 74, 6903-6912 (2014)

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Abstract
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Although in vivo targeting of tumors using fluorescently-labeled probes has greatly gained in importance over the last few years, most of the clinically applied reagents lack tumor cell specificity. 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. Due to the rapid turn-over rate of membrane-Hsp70, fluorescently-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 to the commercially available non-peptide small molecule alpha v beta3-integrin antagonist IntegriSense (trademark), TPP exhibits a significantly higher tumor-to-background contrast and stronger tumor-specific signal intensity in all tested tumor models. Moreover, in contrast to IntegriSense (trademark), 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-specific drug delivery and other Hsp70- based targeted therapies.

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