title: Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone.
abstract: This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected (125)I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting (125)I-labeled PSA30. Tissue uptake of (125)I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, (18)F-fluoro-deoxy-glucose ((18)F-FDG) or (18)F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high (125)I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either (18)F-FDG or (18)F-choline. Biodistribution of (125)I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24-48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
authors.affiliation: Division of Urological Cancers, Department of Clinical Sciences, Lund University, Malmö, Sweden. susan.evans-axelsson@med.lu.se
authors.forename: Susan
authors.initials: S
authors.lastname: Evans-Axelsson
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.forename: Anders
authors.initials: A
authors.lastname: Örbom
authors.forename: Pernilla
authors.initials: P
authors.lastname: Peterson
authors.forename: Olle
authors.initials: O
authors.lastname: Nilsson
authors.forename: Johan
authors.initials: J
authors.lastname: Wennerberg
authors.forename: Joanna
authors.initials: J
authors.lastname: Strand
authors.forename: Karin
authors.initials: K
authors.lastname: Wingårdh
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Zandra
authors.initials: Z
authors.lastname: Hagman
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Strand
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000000981:diagnostic imaging*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001345:Autoradiography; D002794:Choline; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging*; D016719:Radioimmunodetection; D019275:Radiopharmaceuticals
chemical_list: D000911:Antibodies, Monoclonal; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D017430:Prostate-Specific Antigen; D002794:Choline