Evaluation of the Metabolic Response to Cyclopamine Therapy in Pancreatic Cancer Xenografts Using a Clinical PET-CT System

Abstract

We analyzed the effects of anti-hedgehog signaling on the (18)F-FDG uptake of pancreatic cancer xenografts (PCXs) using a clinically implemented positron emission tomography (PET)-computer tomography (CT) scanner with high-resolution reconstruction. PCXs from two pancreatic cancer cell lines were developed subcutaneously in nude mice and injected intraperitoneally with a low dose of cyclopamine for 1 week. (18)F-FDG PET-CT was performed using a new-generation clinical PET-CT scanner with minor modifications of the scanning protocol to adapt for small-animal imaging. The data set was reconstructed and quantified using a three-dimensional workstation. MiaPaCa-2 cells, which respond to cyclopamine, showed decreased (18)F-FDG uptake without a change in tumor size. For hip tumors, the maximum standardized uptake value (SUV(max)) was reduced by -24.5 ± 9.2%, the average SUV (SUV(avg)) by -33.5 ± 7.0%, and the minimum SUV (SUV(min)) by -54.4 ± 11.5% (P < .05). For shoulder tumors, SUV(max) was reduced by -14.7 ± 7.5%, SUV(avg) by -12.6 ± 6.3, and SUV(min) by -30.3 ± 16.7% (P < .05). Capan-1 cells, which do not respond to cyclopamine, did not show significant SUV changes. The new generations of clinically implemented PET-CT scanners with high-resolution reconstruction detect a minimal response of PCX to low-dose short-term cyclopamine therapy without changes in tumor size and offer potential for preclinical translational imaging.