Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.
Författare
Summary, in English
The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.
Avdelning/ar
- Urologisk cancerforskning, Malmö
- Medicinsk strålningsfysik, Lund
- Bröstcancer-genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Lund University Bioimaging Center
- EpiHealth: Epidemiology for Health
Publiceringsår
2014
Språk
Engelska
Sidor
311-323
Publikation/Tidskrift/Serie
American journal of nuclear medicine and molecular imaging
Volym
4
Issue
4
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
e-Century Publishing
Ämne
- Radiology, Nuclear Medicine and Medical Imaging
Status
Published
Forskningsgrupp
- Urological cancer, Malmö
ISBN/ISSN/Övrigt
- ISSN: 2160-8407