HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

In vivo MR/optical imaging for gastrin releasing peptide receptor of prostate cancer tumor using Gd-TTDA-NP-BN-Cy5.5.

Abstract
Magnetic resonance imaging (MRI) has become the leading imaging tool for providing fine anatomical and physiology details. Optical imaging is offering a sensitive and specific method for in vivo molecular imaging of targeting molecules. The goal of this study is to design, synthesize, and characterize a new target-specific dual contrast agent for MR and optical imaging. Hence, [Gd(TTDA-NP)(H(2)O)](2-) was prepared and characterized. In addition, an 8-amino acid Bombesin analogue (BN) peptide substrate, which can target prostate, breast, and colon cancer, was synthesized by solid-phase peptide synthesis and subsequently conjugated with [Gd(TTDA-NP)(H(2)O)](2-) to form BN conjugated Gd-TTDA-NP-BN. The water-exchange rate (k(ex)(298)) for [Gd(TTDA-NP)(H(2)O)](2-) (110×10(6)s(-1)) is significantly higher than that of [Gd(DTPA)(H(2)O)](2-) complex and the rotational correlation time (τ(R)) for [Gd(TTDA-NP)(H(2)O)](2-) (145ps) is also higher than those of [Gd(TTDA)(H(2)O)](2-) (104ps) and [Gd(DTPA)(H(2)O)](2-) (103ps). The Gd-TTDA-NP-BN shows remarkable high relaxivity (7.12mM(-1)s(-1)) comparing to that of [Gd(TTDA-NP)(H(2)O)](2-). The fluorescence studies showed that the Gd-TTDA-NP-BN could efficiently enter PC-3 cells. Additionally, the human cancer cells xenografts using Gd-TTDA-NP-BN-Cy5.5 as an optical imaging probe clearly visualized subcutaneous PC-3 tumor and demonstrated its targeting ability to the gastrin releasing peptide (GRP) receptor overexpression. Furthermore, the biodistribution studies demonstrated significantly high tumor uptake (25.97±1.07% ID/g) and high tumor-to-normal tissue ratios at one hour post-injection of Gd-TTDA-NP-BN-Cy5.5 in the animal model. These results suggest that the Gd-TTDA-NP-BN-Cy5.5 is a superior probe for in vivo optical imaging. Importantly, the MR imaging studies showed notable signal enhancement (44.9±4.2%) on the tumor, indicating a high level accumulation of the contrast agent within the PC-3 tumor sites. Hence, targeting of prostate cancer cells was observed under in vitro and in vivo MR imaging studies using Gd-TTDA-NP-BN contrast agent. We conclude that Gd-TTDA-NP-BN and Gd-TTDA-NP-BN-Cy5.5 can be potentially used as the contrast agents for targeting GRP receptor overexpressing cells and tumors.
AuthorsYing-Hsiu Lin, Kasala Dayananda, Chiao-Yun Chen, Gin-Chung Liu, Tsai-Yueh Luo, Hui-Sheng Hsu, Yun-Ming Wang
JournalBioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 19 Issue 3 Pg. 1085-96 (Feb 01 2011) ISSN: 1464-3391 [Electronic] England
PMID20493715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Contrast Media
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • gadolinium 3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid
  • Bombesin
Topics
  • Animals
  • Bombesin (analogs & derivatives, chemical synthesis, pharmacokinetics)
  • Cell Line, Tumor
  • Cell Survival
  • Contrast Media (chemical synthesis, pharmacokinetics)
  • Humans
  • KB Cells
  • Luminescence
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Organometallic Compounds (chemical synthesis, pharmacokinetics)
  • Prostatic Neoplasms (diagnosis)
  • Radiopharmaceuticals
  • Receptors, Bombesin (analysis)
  • Spectroscopy, Near-Infrared

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: