402 LILY OF THE VALLEY FRAGRANCE CONTRAST AGENTS FOR PROSTATE CANCER SPECIFIC IMAGING

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011402 LILY OF THE VALLEY FRAGRANCE CONTRAST AGENTS FOR PROSTATE CANCER SPECIFIC IMAGING Stefan Heckl, Jörg Hennenlotter, Arnulf Stenzl, and Christian Schwentner Stefan HecklStefan Heckl Tübingen, Germany More articles by this author , Jörg HennenlotterJörg Hennenlotter Tübingen, Germany More articles by this author , Arnulf StenzlArnulf Stenzl Tübingen, Germany More articles by this author , and Christian SchwentnerChristian Schwentner Tübingen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.491AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The detection of lymph node metastases is decisive for the prognosis and therapeutic strategy in patients suffering from prostate cancer. However, the specific identification of prostate cancer lymph node metastases by magnetic resonance imaging (MRI) is not possible and biopsies are necessary. We found that the lily of the valley fragrance receptor (human odorant receptor hOR 17-4) is highly expressed on prostate cancer cells. Undecylic aldehyde is the antagonist of bourgeonal, which binds to the lily of the valley fragrance receptor. Until now no activating or inhibitory ligands of odorant receptors have found use in cancer diagnostics. METHODS We synthesized conjugates containing bourgeonal or undecylic aldehyde, gadolinium-diethylenetriamine pentaacetic acid (DTPA) (a common magnetic resonance contrast agent) and rhodamine isothiocyanate (RITC) (a fluorescent dye). The LNCaP prostate cancer cell line as well as three other non-prostate malignant cell lines [colon cancer (Colo205), glioma (U373), osteosarcoma (U2OS)] were incubated with these conjugates and evaluated by fluorescence-activated cell sorting (FACS), confocal laser scanning microscopy (CLSM) and MRI. The expression of the lily of the valley fragrance receptor was determined by real-time polymerase chain reaction. In vivo MRI after intravenous conjugate application was performed on nude mice bearing human prostate cancer LNCaP xenografts. Frozen sections from the organs and the tumors were investigated by CLSM. RESULTS FACS and CLSM showed that the rhodamine-labelled conjugates specifically and strongly stained LNCaP prostate cancer cells whereas other malignant non-prostate cells were not markedly stained. No cytotoxic effects were seen even after long time incubation for 48 hours. In MRI prostate cancer cells could be differentiated from the other cancer cells upon their shorter relaxation times (higher signal intensity) after incubation with the conjugates. A high hOR17-4 mRNA expression level was only found on prostate cancer cells. In vivo MRI revealed that the conjugates were well tolerated and specifically taken up into the human prostate cancer xenografts. The conjugates accumulated within the cytoplasm of LNCaP prostate cancer cells in vivo as could be shown by CLSM. CONCLUSIONS The novel conjugates demonstrated high prostate cancer cell specificity in vitro. First in vivo experiments indicate their pontential use for future prostate cancer specific MRI especially for the demarkation of prostate cancer lymph node metastases. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e162-e163 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stefan Heckl Tübingen, Germany More articles by this author Jörg Hennenlotter Tübingen, Germany More articles by this author Arnulf Stenzl Tübingen, Germany More articles by this author Christian Schwentner Tübingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...