MRI of transgene expression: correlation to therapeutic gene expression.
Magnetic resonance imaging (MRI) can provide high-resolution 3D maps of structural and functional information, yet its use of mapping in vivo gene expression has only recently been explored. A potential application for this technology is to noninvasively image transgene expression. The current study explores the latter using a nonregulatable internalizing engineered transferrin receptor (ETR) whose expression can be probed for with a superparamagnetic Tf-CLIO probe. Using an HSV-based amplicon vector system for transgene delivery, we demonstrate that: 1) ETR is a sensitive MR marker gene; 2) several transgenes can be efficiently expressed from a single amplicon; 3) expression of each transgene results in functional gene product; and 4) ETR gene expression correlates with expression of therapeutic genes when the latter are contained within the same amplicon. These data, taken together, suggest that MRI of ETR expression can serve as a surrogate for measuring therapeutic transgene expression.
Ichikawa
Tomotsugu
T
Neurosurgical Service and Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Högemann
Dagmar
D
Saeki
Yoshinaga
Y
Tyminski
Edyta
E
Terada
Kinya
K
Weissleder
Ralph
R
Chiocca
E Antonio
EA
Basilion
James P
JP
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D018773:Genes, erbB-1 / Q000502:physiology; D005819:Genetic Markers; D005822:Genetic Vectors; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006561:Herpes Simplex / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007501:Iron / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D015335:Molecular Probes; D010087:Oxides / Q000493:pharmacokinetics; D011990:Receptors, Transferrin / Q000235:genetics*; D012190:Retroviridae; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics*; D014407:Tumor Cells, Cultured
D003287:Contrast Media; D005819:Genetic Markers; D015335:Molecular Probes; D010087:Oxides; D011990:Receptors, Transferrin; D003577:Cytochrome P-450 Enzyme System; D007501:Iron