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.


