title: Synthesis and pre-clinical evaluation of an (18)F-labeled single-chain antibody fragment for PET imaging of epithelial ovarian cancer.
abstract: Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is currently no molecular imaging probe in the clinic for the assessment of CA125 expression in vivo. The present study describes the development of an (18)F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in E.coli. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of (18)F-labeled scFv-B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]FBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.).
authors: Department of Oncology, Cross Cancer Institute, University of AlbertaEdmonton, AB, T6G 1Z2, Canada; Faculty of Pharmacy and Pharmaceutical Sciences, Katz Centre for Pharmacy and Health Research, University of AlbertaEdmonton, AB, T6G 2E1, Canada.
authors: Sai Kiran
authors: SK
authors: Sharma
authors: Department of Oncology, Cross Cancer Institute, University of Alberta Edmonton, AB, T6G 1Z2, Canada.
authors: Melinda
authors: M
authors: Wuest
authors: Department of Oncology, Cross Cancer Institute, University of Alberta Edmonton, AB, T6G 1Z2, Canada.
authors: Jenilee D
authors: JD
authors: Way
authors: Department of Oncology, Cross Cancer Institute, University of Alberta Edmonton, AB, T6G 1Z2, Canada.
authors: Vincent R
authors: VR
authors: Bouvet
authors: Department of Oncology, Cross Cancer Institute, University of Alberta Edmonton, AB, T6G 1Z2, Canada.
authors: Monica
authors: M
authors: Wang
authors: Department of Oncology, Cross Cancer Institute, University of AlbertaEdmonton, AB, T6G 1Z2, Canada; Faculty of Pharmacy and Pharmaceutical Sciences, Katz Centre for Pharmacy and Health Research, University of AlbertaEdmonton, AB, T6G 2E1, Canada.
authors: Frank R
authors: FR
authors: Wuest
keywords: CA125; epithelial ovarian cancer; fluorine-18; positron emission tomography