title: Biologically-targeted detection of primary and micro-metastatic ovarian cancer.
abstract: Ovarian cancer is the leading cause of morbidity/mortality from gynecologic malignancy. Early detection of disease is difficult due to the propensity for ovarian cancer to disseminate throughout the peritoneum. Currently, there is no single accurate test to detect primary or recurrent ovarian cancer. We report a novel clinical strategy using PPF: a multimodal, PET and optical, folate receptor (FR)-targeted agent for ovarian cancer imaging. The capabilities of PPF were evaluated in primary human ovarian cancer cells, in vivo xenografts derived from primary cells and ex vivo patient omemtum, as the heterogeneity and phenotype displayed by patients is retained. Primary cells uptake PPF in a FR-dependent manner demonstrating approximately a 5- to 25-fold increase in fluorescence. By both PET and fluorescence imaging, PPF specifically delineated FR-positive, ovarian cancer xenografts, with similar tumor-to-background ratios of 8.91±0.91 and 7.94±3.94, and micro-metastatic studding (<1mm), which demonstrated a 3.5-fold increase in PPF uptake over adjacent normal tissue. Ex vivo patient omentum demonstrated selective uptake of PFF by tumor deposits. The ability of PPF to identify metastatic deposits <1mm could facilitate more complete debulking (currently, optimal debulking is <10mm residual tumor), by providing a more sensitive imaging strategy improving treatment planning, response assessment and residual/recurrent disease detection. Therefore, PPF is a novel clinical imaging strategy that could substantially improve the prognosis of patients with ovarian cancer by allowing pre-, post- and intra-operative tumor monitoring, detection and possibly treatment throughout all stages of therapy and tumor progression.
authors.affiliation: Department of Medical Biophysics, Princess Margarete Cancer Center, University of Toronto, Toronto, Canada.
authors.forename: Tracy W
authors.initials: TW
authors.lastname: Liu
authors.forename: Jocelyn M
authors.initials: JM
authors.lastname: Stewart
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Macdonald
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Blaise
authors.initials: B
authors.lastname: Clarke
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005260:Female; D058975:Folate Receptor 1 / Q000032:analysis*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D013194:Staining and Labeling / Q000379:methods*
chemical_list: D058975:Folate Receptor 1; D002734:Chlorophyll; C040298:pyropheophorbide a; D005492:Folic Acid
keywords: Folate Receptor; Ovarian Cancer; PET; fluorescence imaging; multimodal.