1311 DEVELOPMENT OF A NOVEL NANOENCAPSULATED CONTRAST AGENT DELIVERED INTRACELLULARLY TO ENHANCE MR IMAGING OF PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 20121311 DEVELOPMENT OF A NOVEL NANOENCAPSULATED CONTRAST AGENT DELIVERED INTRACELLULARLY TO ENHANCE MR IMAGING OF PROSTATE CANCER Joel Slaton, Bruce Hammer, Gregory Metzger, and Gretchen Unger Joel SlatonJoel Slaton Minneapolis, MN More articles by this author , Bruce HammerBruce Hammer Minneapolis, MN More articles by this author , Gregory MetzgerGregory Metzger Minneapolis, MN More articles by this author , and Gretchen UngerGretchen Unger Chaska, MN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1658AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Systemic MR contrast agents, whether traversing primarily in the extracellular compartments or attaching onto the cell surface, can enhance imaging of tumor anatomy. However, these agents are nonspecific and cannot always differentiate between neoplastic and normal tissue. We have developed a novel contrast agent encapsulating dysprosium dextran (DyDex) into sub-50 nanometer capsule, a delivery technology capable of intracellular delivery of large cargos in a tissue- and cell-specific manner. We present our preliminary work demonstrating the ability of this agent to provide an intracellular positive signal on T1-weighted MR imaging of prostate cancer. METHODS DyDex (which provides a positive MR signal on T1 imaging) was incorporated into nanocapsules coated with tenfibgen which selectively targets integrins. It was discovered Dy retained red fluorescence within the hydrophobic inner environment of the s50 capsule. We performed in vitro and in vivo toxicity studies. We conducted pilot imaging studies in male mice bearing the lymph node-metastatic tumor model, PC3LN4 with DyDex encapsulated in s50 tenfibgen capsules. Mice were imaged using a 5 T scanner with a spin echo sequence. RESULTS PC3LN4 cells were treated with PBS suspensions of 1) naked DyDex 2) naked Gd-DTPA or 3) s50 Tbg capsules bearing DyDex and assessed for cell growth by thymidine incorporation. s50 encapsulated DyDextran showed no negative impact on growth vs. naked Dy3+ ion. For in vivo assessment, male mice received single i.v. injections of DyDex and controls. The results indicate that the s50 capsules at a 10x dose (5 umol/kg) did not significantly perturb the blood chemistry or hematology values (p < 0.05). Imaging demonstrated that good tumor contrast was still apparent at 10 nmol/kg equivalent to a dose of 50 ng of DyDex in prostatic PC3-LN4 flank tumor. This dosage level is 10,000-fold less than standard gadolinium dose of 0.1 mmol/kg which has been associated with significant kidney toxicity in some patients. Two mm lymph node masses were easily seem at 5T MR. Bright nuclear red signal that colocalized in confocal images with cytoplasmic capsule signal was observed in 10 nmol/kg-treated primary tumor and 100 nmol/kg-treated primary tumor and lymph node metastases. CONCLUSIONS We have demonstrated intracellular nontoxic uptake of a novel nanoencapsulated DyDex agent with corresponding positive T1-weighted signal on MRI in human prostate cancer xenografts. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e531 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joel Slaton Minneapolis, MN More articles by this author Bruce Hammer Minneapolis, MN More articles by this author Gregory Metzger Minneapolis, MN More articles by this author Gretchen Unger Chaska, MN More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...