Imaging pancreatic cancer with a peptide-nanoparticle conjugate targeted to normal pancreas.
Designing molecules that bind to targets that become upregulated or overexpressed as normal cells become cancerous is an important strategy for both therapeutic and diagnostic drug design. We hypothesized that pancreatic ductal 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 fluorescein hapten visualization method to assess the presence of bombesin (BN) receptors, we first demonstrated BN receptors in the normal mouse and human pancreas, but then the lack of BN binding receptors in 13 out of 13 specimens of PDAC. The BN peptide-nanoparticle conjugate, BN-CLIO(Cy5.5), was synthesized and accumulated in the mouse pancreas in receptor dependent fashion, but not in a receptor dependent fashion in other tissues, based on tissue fluorescence measurements. The BN-CLIO(Cy5.5) nanoparticle decreased the T2 of normal pancreas and enhanced 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.
Montet
Xavier
X
Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Weissleder
Ralph
R
Josephson
Lee
L
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000595:Amino Acid Sequence; D006801:Humans; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D053758:Nanoparticles; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism