title: Highly specific PET imaging of prostate tumors in mice with an iodine-124-labeled antibody fragment that targets phosphatidylserine.
abstract: Phosphatidylserine (PS) is an attractive target for imaging agents that identify tumors and assess their response to therapy. PS is absent from the surface of most cell types, but becomes exposed on tumor cells and tumor vasculature in response to oxidative stresses in the tumor microenvironment and increases in response to therapy. To image exposed PS, we used a fully human PS-targeting antibody fragment, PGN635 F(ab')2, that binds to complexes of PS and β2-glycoprotein I. PGN635 F(ab')2 was labeled with the positron-emitting isotope iodine-124 ((124)I) and the resulting probe was injected into nude mice bearing subcutaneous or orthotopic human PC3 prostate tumors. Biodistribution studies showed that (124)I-PGN635 F(ab')2 localized with remarkable specificity to the tumors with little uptake in other organs, including the liver and kidneys. Clear delineation of the tumors was achieved by PET 48 hours after injection. Radiation of the tumors with 15 Gy or systemic treatment of the mice with 10 mg/kg docetaxel increased localization in the tumors. Tumor-to-normal (T/N) ratios were inversely correlated with tumor growth measured over 28 days. These data indicate that (124)I-PGN635 F(ab')2 is a promising new imaging agent for predicting tumor response to therapy.
authors.affiliation: Department of Pharmacology, The Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Stafford
authors.affiliation: Department of Radiology, The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Hao
authors.affiliation: Department of Pharmacology, The Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Best
authors.affiliation: Department of Radiology, The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, The Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Thorpe
mesh_terms: D000818:Animals; D000077143:Docetaxel; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010718:Phosphatidylserines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D043823:Taxoids; D053482:beta 2-Glycoprotein I / Q000378:metabolism
chemical_list: D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D010718:Phosphatidylserines; D043823:Taxoids; D053482:beta 2-Glycoprotein I; D000077143:Docetaxel