Stephanie Kay Carlson MD, Presenter: Royalties, Medspira, LLC

Alan Penheiter PhD, Abstract Co-Author: Nothing to Disclose

Claire E. Bender MD, Abstract Co-Author: Nothing to Disclose

Sibel Erdogan, Abstract Co-Author: Nothing to Disclose

Stephen J. Murphy PhD, Abstract Co-Author: Nothing to Disclose

Steven N. Hart PhD, Abstract Co-Author: Nothing to Disclose

Joema Felipe Lima, Abstract Co-Author: Nothing to Disclose

Fariborz (Fred) Rakhshan Rohakhtar, Abstract Co-Author: Nothing to Disclose

Daniel R. O'Brien, Abstract Co-Author: Nothing to Disclose

William Bamlet MS, Abstract Co-Author: Nothing to Disclose

Ryan E. Wuertz, Abstract Co-Author: Nothing to Disclose

Thomas C. Smyrk, Abstract Co-Author: Nothing to Disclose

Fergus J. Couch PhD, Abstract Co-Author: Nothing to Disclose

George Vasmatzis PhD, Abstract Co-Author: Nothing to Disclose

Imaging plays an important role in the management of patients with pancreatic ductal adenocarcinoma (PDAC); however, the ability to reliably detect early stage tumors and accurately identify the true extent of disease preoperatively is severely limited with current anatomical diagnostic imaging techniques (computed tomography, magnetic resonance imaging, endoscopic ultrasound). We employed a target-centric strategy to identify transporter proteins upregulated in PDAC versus normal pancreas as potential targets for a new functional imaging probe to complement existing anatomical imaging approaches.

We have performed transcriptomic (gene expression) profiling using laser capture microdissection, microarray and RNAseq on histologically-confirmed primary PDAC tumors and normal pancreas tissue from 33 patients, including five patients whose tumors were isoattenuating to normal pancreas and not visible on CT. RNAseq data were analyzed as gene normalized counts using the mapped reads per kilobase per million mapped reads (RPKM) method. Target expression at the protein level was confirmed with immunohistochemistry on tissue microarrays from 94 PDAC patients. All studies on human specimens were approved by our Institutional Review Board.

Our search has identified at least 10 candidate transporter proteins upregulated in PDAC versus normal pancreas. Thus far, the best potential imaging target identified was SLC6A14, a neutral and basic amino acid transporter. SLC6A14 was overexpressed at the transcriptional level in all patients and expressed at the protein level in 95% of PDAC tumors.

SLC6A14 merits further investigation as a candidate transporter for functional imaging of PDAC.

A new functional imaging probe that selectively targets PDAC with high sensitivity could transform patient management by allowing earlier detection and surgical intervention, and improving preoperative staging of disease.

Carlson, S, Penheiter, A, Bender, C, Erdogan, S, Murphy, S, Hart, S, Lima, J, Rohakhtar, F, O'Brien, D, Bamlet, W, Wuertz, R, Smyrk, T, Couch, F, Vasmatzis, G, Transcriptomic and Immunohistochemical Profiling of Pancreatic Ductal Adenocarcinoma: Search for Functional Imaging Biomarkers.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14006767.html