title: [(18)F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments.
abstract: Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer. Mice bearing LAPC4-CR subcutaneous tumors were administered [(18)F]-FDG via intravenous injection. After a 60-minute distribution phase, the mice were imaged on a PET/CT scanner with submillimeter resolution; and the fused PET/CT images were analyzed to evaluate tumor size, location, and metabolism across the cohort of mice. The xenograft tumors showed [(18)F]-FDG uptake that was independent of tumor size and was significantly greater than uptake in skeletal muscle and liver in mice (Wilcoxon signed-rank P values of .0002 and .0002, respectively). [(18)F]-FDG metabolism of the LAPC4-CR tumors was 2.1 ± 0.8 ID/cm(3)*wt, with tumor to muscle ratio of 7.4 ± 4.7 and tumor to liver background ratio of 6.7 ± 2.3. Noninvasive molecular imaging techniques such as PET/CT can be used to probe the microenvironment of tumors in vivo. This study showed that [(18)F]-FDG-PET/CT could be used to image and assess glucose metabolism of LAPC4-CR xenografts in vivo. Further work can investigate the use of PET/CT to quantify the metabolic response of LAPC4-CR to novel agents and combination therapies using soft tissue and possibly bone compartment xenograft models.
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Center for Biomedical Imaging in Oncology (Lurie Family Imaging Center), Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA. Electronic address: kmccall@partners.org.
authors.forename: Keisha C
authors.initials: KC
authors.lastname: McCall
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Cheng
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Biomedical Imaging in Oncology (Lurie Family Imaging Center), Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kohl
authors.affiliation: Center for Biomedical Imaging in Oncology (Lurie Family Imaging Center), Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Tupper
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Center for Biomedical Imaging in Oncology (Lurie Family Imaging Center), Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston MA 02115, USA.
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van den Abbeele
authors.affiliation: Department of Medical Imaging, Sunnybrook Hospital, University of Toronto, 263 McCaul St-4th Floor, Toronto, Ontario M5T 1W7, Canada.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Zukotynski
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston MA 02115, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney