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


RESULTS
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.


CONCLUSIONS
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.
Flores
Leo Garcia
LG
Department of Experimental Diagnostic Imaging, Center for Advanced Biomedical Imaging Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Bertolini
Susanna
S
Yeh
Hsin Hsin
HH
Young
Daniel
D
Mukhopadhyay
Uday
U
Pal
Ashutosh
A
Ying
Yunming
Y
Volgin
Andrei
A
Shavrin
Aleksandr
A
Soghomonyan
Suren
S
Tong
William
W
Bornmann
William
W
Alauddin
Mian M
MM
Logsdon
Craig
C
Gelovani
Juri G
JG
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D018267:Carcinoma, Acinar Cell / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000494:pharmacology*; D007785:Lactose / Q000494:pharmacology* / Q000031:analogs & derivatives; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D000073718:Pancreatitis-Associated Proteins; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D037181:Lectins, C-Type; D008024:Ligands; C548885:O-galactopyranosyl-(1-4')-2'-deoxy-2'-fluoroethylglucopyranose; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D019275:Radiopharmaceuticals; D007785:Lactose