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

Ying Hsiu Lin, Kasala Dayananda, Chiao Yun Chen, Gin Chung Liu, Tsai Yueh Luo, Hui Sheng Hsu, Yun-Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 (kex298) 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- (145 ps) is also higher than those of [Gd(TTDA)(H 2 O)] 2- (104 ps) and [Gd(DTPA)(H 2 O)] 2- (103 ps). The Gd-TTDA-NP-BN shows remarkable high relaxivity (7.12 mM -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.

Original languageEnglish
Pages (from-to)1085-1096
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number3
DOIs
StatePublished - 1 Feb 2011

Keywords

  • Bombesin
  • Fluorescence
  • Gastrin releasing peptide (GRP) receptor
  • Magnetic resonance imaging
  • Peptide

Fingerprint Dive into the research topics of 'In vivo MR/optical imaging for gastrin releasing peptide receptor of prostate cancer tumor using Gd-TTDA-NP-BN-Cy5.5'. Together they form a unique fingerprint.

Cite this