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 language | English (US) |
|---|---|
| Pages (from-to) | 1006-1011 |
| Number of pages | 6 |
| Journal | Magnetic Resonance Imaging |
| Volume | 31 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jul 2013 |
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Keywords
- β-galactosidase
- H MRI
- Fe-chelation
- Gene reporters
- LacZ
- Signal enhancement
- T
- T
ASJC Scopus subject areas
- Biophysics
- Radiology Nuclear Medicine and imaging
- Biomedical Engineering
Cite this
Novel S-Gal® analogs as 1H MRI reporters for in vivo detection of β-galactosidase. / Gulaka, Praveen K.; Yu, Jian Xin; Liu, Li; Mason, Ralph P.; Kodibagkar, Vikram.
In: Magnetic Resonance Imaging, Vol. 31, No. 6, 07.2013, p. 1006-1011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel S-Gal® analogs as 1H MRI reporters for in vivo detection of β-galactosidase
AU - Gulaka, Praveen K.
AU - Yu, Jian Xin
AU - Liu, Li
AU - Mason, Ralph P.
AU - Kodibagkar, Vikram
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - β-galactosidase
KW - H MRI
KW - Fe-chelation
KW - Gene reporters
KW - LacZ
KW - Signal enhancement
KW - T
KW - T
UR - http://www.scopus.com/inward/record.url?scp=84878658315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878658315&partnerID=8YFLogxK
U2 - 10.1016/j.mri.2013.03.001
DO - 10.1016/j.mri.2013.03.001
M3 - Article
C2 - 23602729
AN - SCOPUS:84878658315
VL - 31
SP - 1006
EP - 1011
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
SN - 0730-725X
IS - 6
ER -