Detection of Syndecan-1 probe localization to pancreatic adenocarcinoma using multispectral optoacoustic tomography

Objectives The insulin-like growth factor 1 receptor is over-expressed in pancreatic cancer, and has been shown to associate with Syndecan-1. The objective of this study was to evaluate Syndecan-1 as a molecular probe to target pancreatic cancer in vivo using multispectral optoacoustic tomography.

Methods IGFR-1 expression on multiple pancreatic cell lines was compared using Western blot against positive and negative controls. In vitro binding of Syndecan-1 was evaluated on flow cytometry. S2VP10 cells were then orthotopically implanted into the pancreas of SCID mice. After tumors developed, the mice were then intravenously injected with Syndecan-1 probe and tumor uptake of probe was evaluated with multispectral optoacoustic tomography (MSOT). Probe uptake was verified ex vivo using traditional planar fluorescent imaging.

Results IGF1-R expression was increased on aggressive pancreatic cancer cell lines. Flow cytometry of S2VP10 cells exposed to Syndecan-1 probe demonstrated partial binding of syndecan-1, although this did not appear to be mediated through IGF1-R. Upon intravenous injection of Syndecan-1 probe into the mice, in vivo probe accumulation within the pancreatic tumor was seen with MSOT 6 hours after injection. Probe signal was concentrated within the tumor with minimal off-target effects. Ex vivo fluorescent imaging confirmed the in vivo findings.

Conclusions Orthotopic pancreas tumors were detected using Syndecan-1 probe as a contrast agent via MSOT at depths >5mm. Syndecan-1 probe selectively binds to pancreatic adenocarcinoma, and could be used as a ligand in the development of targeted therapies and molecular imaging.

Research Support This work was supported by NIH grant CA135090.