| Abstract
| - Designing molecules that bind to targets that become upregulated or overexpressed as normal cells becomecancerous is an important strategy for both therapeutic and diagnostic drug design. We hypothesized that pancreaticductal adenocarcinoma (PDAC) might be imaged with the inverse strategy, that is by the design of a nanoparticle−conjugate targeted to bombesin (BN) receptors present on normal acinar cells of the pancreas. Using the fluoresceinhapten visualization method to assess the presence of bombesin (BN) receptors, we first demonstrated BN receptorsin the normal mouse and human pancreas, but then the lack of BN binding receptors in 13 out of 13 specimensof PDAC. The BN peptide−nanoparticle conjugate, BN−CLIO(Cy5.5), was synthesized and accumulated in themouse pancreas in receptor dependent fashion, but not in a receptor dependent fashion in other tissues, based ontissue fluorescence measurements. The BN−CLIO(Cy5.5) nanoparticle decreased the T2 of normal pancreas andenhanced the ability to visualize tumor in a model of pancreatic cancer by MRI. The use of BN−CLIO(Cy5.5)nanoparticle as a normal tissue-targeted, T2-reducing contrast agent offers a promising approach to imaging PDAC.
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