Novel S-Gal® analogs as 1H MRI reporters for in vivo detection of β-galactosidase

Praveen K. Gulaka, Jian Xin Yu, Li Liu, Ralph P. Mason, Vikram Kodibagkar

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The quantitative assessment of gene expression and related enzyme activity in vivo could be important for the characterization of gene altering diseases and therapy. The development of imaging techniques, based on specific reporter molecules may enable routine non-invasive assessment of enzyme activity and gene expression in vivo. We recently reported the use of commercially available S-Gal® as a β-galactosidase reporter for 1H MRI, and the synthesis of several S-Gal® analogs with enhanced response to β-galactosidase activity. We have now compared these analogs in vitro and have identified the optimal analog, C3-GD, based on strong T1 and T2 response to enzyme presence (δR1 and δR2~1.8 times S-Gal®). Moreover, application is demonstrated in vivo in human breast tumor xenografts. MRI studies in MCF7-lacZ tumors implanted subcutaneously in athymic nude mice (n=6), showed significant reduction in T1 and T2 values (each~13%) 2h after intra-tumoral injection of C3-GD, whereas the MCF7 (wild type) tumors showed slight increase. Thus, C3-GD successfully detects β-galactosidase activity in vivo and shows promise as a lacZ gene 1H MR reporter molecule.

Original languageEnglish (US)
Pages (from-to)1006-1011
Number of pages6
JournalMagnetic Resonance Imaging
Volume31
Issue number6
DOIs
StatePublished - Jul 2013

Keywords

  • Fe-chelation
  • Gene reporters
  • H MRI
  • LacZ
  • Signal enhancement
  • T
  • T
  • β-galactosidase

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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