Preliminary evaluation of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for detection of pancreatic cancer in nude mouse orthotopic xenografts

Introduction: Early detection of pancreatic cancer could save many thousands of lives. Non-invasive diagnostic imaging, including PET with [F-18]FDG, has inadequate resolution for detection of small (2-3 mm) pancreatic tumours. We demonstrated the efficacy of PET imaging with an F-18-labelled lactose derivative, [F-18]FEDL, that targets HIP/PAP, a biomarker that is overexpressed in the peritumoural pancreas. We developed another analogue, 1-[F-18]fluoroethyl lactose ([F-18]FEL), which is simpler to synthesise, for the same application. We conducted a preliminary evaluation of the new probe and its efficacy in detecting orthotopic pancreatic carcinoma xenografts in mice. Methods: Xenografts were developed in nude mice by injecting L3.6pl/GL(+) pancreatic carcinoma cells into the pancreas of each mouse. Tumour growth was monitored by bioluminescence imaging (BLI); accuracy of BLI tumour size estimates was verified by MRI in two representative mice. When the tumour size reached approximately 2-3 mm, the animals were injected with [F-18]FEL (3.7 MBq) and underwent static PET/CT scans. Blood samples were collected at 2, 5, 10, 20 and 60 min after [F-18]FEL injection to track blood clearance. Following imaging, animals were sacrificed and their organs and tumours/pancreatic tissue were collected and counted on a gamma counter. Pancreas, including tumour, was frozen, sliced and used for autoradiography and immunohistochemical analysis of HIP/PAP expression. Results: Tumour growth was rapid, as observed by BLI and MRI. Blood clearance of [F-18]FEL was hi-exponential, with half-lives of approximately 3.5 min and 40 min. Mean accumulation of [18F]FEL in the peritumoural pancreatic tissue was 129 +/- 0.295 %ID/g, and that in the normal pancreas of control animals was 0.090 +/- 0.101 %ID/g. [F-18]FEL was cleared predominantly by the kidneys. Comparative analysis of autoradiographic images and immunostaining results demonstrated a correlation between [F-18]FEL binding and HIP/PAP expression. Conclusion: [F-18]FEL may be useful for non-invasive imaging of early-stage pancreatic turnouts by PET. The results warrant further studies. (c) 2014 Elsevier Inc. All rights reserved.