Abstract
BackgroundEarly diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. Current non-invasive diagnostic imaging techniques have inadequate resolution and sensitivity for detection of small size (∼2–3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with β-O-D-galactopyranosyl-(1,4′)-2′-deoxy-2′-[18F]fluoroethyl-D-glucopyranose ([18F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [18F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.Methodology/Principal FindingsDynamic PET/CT imaging demonstrated rapid accumulation of [18F]FEDL in peritumoral pancreatic tissue (4.04±2.06%ID/g), bi-exponential blood clearance with half-lives of 1.65±0.50 min and 14.14±3.60 min, and rapid elimination from other organs and tissues, predominantly by renal clearance. Using model-independent graphical analysis of dynamic PET data, the average distribution volume ratio (DVR) for [18F]FEDL in peritumoral pancreatic tissue was estimated as 3.57±0.60 and 0.94±0.72 in sham-operated control pancreas. Comparative analysis of quantitative autoradiographic images and densitometry of immunohistochemically stained and co-registered adjacent tissue sections demonstrated a strong linear correlation between the magnitude of [18F]FEDL binding and HIP/PAP expression in corresponding regions (r = 0.88). The in situ analysis demonstrated that at least a 2–4 fold apparent lesion size amplification was achieved for submillimeter tumors and to nearly half a murine pancreas for tumors larger than 3 mm.Conclusion/SignificanceWe have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [18F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [18F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis.
Highlights
The estimated number of new cases of pancreatic cancer in the United States in 2009 is 42,470 and the estimated number of deaths is 35,240 [1]
Conclusion/Significance: We have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [18F]FEDL positron emission tomography and computer tomography (PET/CT) of tumor biomarker hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) over-expressed in peritumoral pancreatic tissue
Based on the IHC analysis of pancreatic tissue sections, the apparent diameter of the lesion based on the expression of HIP/PAP in peritumoral pancreatic tissue ranged from 2 mm for sub-millimeter sized tumors (Fig. 1C) to almost a half of the pancreas (10–12 mm) for tumors of 2–3 mm in diameter
Summary
The estimated number of new cases of pancreatic cancer in the United States in 2009 is 42,470 and the estimated number of deaths is 35,240 [1]. Pancreatic cancer accounts for only 2% of all malignancies, it is the fourth most common cause of cancer death in the United States. Such a poor prognosis for patients with pancreatic cancer is because 80–90% of patients have unresectable disease at the time of diagnosis [2]. Early diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods is very important and could save lives of many thousands of patients, because early detection of small pancreatic cancers is likely to increase resectability rates. Diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. We have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with b-O-D-galactopyranosyl-(1,49)-29-deoxy-29-[18F]fluoroethyl-D-glucopyranose ([18F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [18F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells
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