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 Journal Article
| Authors: | Evans-Axelsson, S.; Ulmert, D.; Örbom, A.; Peterson, P.; Nilsson, O.; Wennerberg, J.; Strand, J.; Wingårdh, K.; Olsson, T.; Hagman, Z.; Tolmachev, V.; Bjartell, A.; Lilja, H.; Strand, S. E. |
| Article 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 125I-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 125I- labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose ( 18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-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. © Copyright 2012, Mary Ann Liebert, Inc. 2012. |
| Keywords: | immunohistochemistry; controlled study; histopathology; nonhuman; cancer staging; positron emission tomography; cancer grading; radiopharmaceuticals; adenocarcinoma; prostate specific antigen; animal cell; mouse; animals; mice; animal tissue; animal experiment; animal model; in vivo study; tumor xenograft; monoclonal antibody; prostate cancer; prostate-specific antigen; prostatic neoplasms; antibodies, monoclonal; iodine 125; iodine radioisotopes; mice, nude; feasibility studies; epitope; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; choline; antibody specificity; prostate adenocarcinoma; neoplasm transplantation; autoradiography; free psa; fluorine radioisotopes; radioimmunodetection; digital autoradiography; dual isotope imaging |
| Journal Title: | Cancer Biotherapy and Radiopharmaceuticals |
| Volume: | 27 |
| Issue: | 4 |
| ISSN: | 1084-9785 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2012-05-01 |
| Start Page: | 243 |
| End Page: | 251 |
| Language: | English |
| DOI: | 10.1089/cbr.2011.1088 |
| PROVIDER: | scopus |
| PMCID: | PMC3353767 |
| PUBMED: | 22489659 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 July 2012" - "CODEN: CBRAF" - "Source: Scopus" |
