Detection of pancreatic carcinomas by imaging lactose-binding protein expression in peritumoral pancreas using [18F]fluoroethyl-deoxylactose PET/CT.

Abstract

BACKGROUND:

Early 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 ( approximately 2-3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with beta-O-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[(18)F]fluoroethyl-D-glucopyranose ([(18)F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [(18)F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.

METHODOLOGY/PRINCIPAL FINDINGS:

Dynamic PET/CT imaging demonstrated rapid accumulation of [(18)F]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 [(18)F]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 [(18)F]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/SIGNIFICANCE:

We have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [(18)F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [(18)F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis.

• Authors: Leo Garcia Flores, Susanna Bertolini, Hsin Hsin Yeh, Daniel Young, Uday Mukhopadhyay, Ashutosh Pal, Yunming Ying, Andrei Volgin, Aleksandr Shavrin, Suren Soghomonyan, William Tong, William Bornmann, Mian M Alauddin, Craig Logsdon, Juri G Gelovani
• Journal: PloS one (PLoS One) Vol. 4 Issue 11 Pg. e7977 (Nov 24 2009) ISSN: 1932-6203 [Electronic] United States
• PMID: 19956730 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Fluorine Radioisotopes
• Lectins, C-Type
• Ligands
• O-galactopyranosyl-(1-4')-2'-deoxy-2'-fluoroethylglucopyranose
• Pancreatitis-Associated Proteins
• REG3A protein, human
• Radiopharmaceuticals
• Lactose

Topics

• Animals
• Antigens, Neoplasm (metabolism)
• Biomarkers, Tumor (metabolism)
• Carcinoma (metabolism)
• Carcinoma, Acinar Cell (metabolism)
• Fluorine Radioisotopes (pharmacology)
• Lactose (pharmacology)
• Lectins, C-Type (metabolism)
• Ligands
• Mice
• Models, Biological
• Neoplasm Transplantation
• Pancreas (metabolism)
• Pancreatic Neoplasms (diagnosis)
• Pancreatitis-Associated Proteins
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (pharmacology)
• Tomography, Emission-Computed, Single-Photon (methods)
• Tomography, X-Ray Computed (methods)