Early gene therapy-induced apoptotic response in BT4C gliomas by magnetic resonance relaxation contrast T1 in the rotating frame.
The design and evaluation of therapeutic gene transfection protocols and vectors are under extensive development. Magnetic resonance imaging (MRI) techniques can aid considerably in the development of experimental treatment approaches, as well as in determining treatment response by observing gross tissue morphology. However, through a unique set of contrast parameters, namely T1, T2, and diffusion, more information about tissue status can be obtained while delineating and classifying tumor characteristics in more detail. We show here that T1 relaxation in the rotating frame, T1rho, provides unique in vivo MRI contrast. Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these tumors, resulted in significantly prolonged T1rho relaxation times in MRI already after 3 days of treatment, whereas conventional contrast parameters were elevated after 6-8 days of therapy. Interestingly, the prolonged T1rho values were observed while an increase in tumor volume was still taking place. The regions of elevated T1rho relaxation coincided with high apoptotic activity as determined by histology, suggesting that T1rho MRI contrast could be used as a novel early indicator of cytotoxic cell damage in gliomas.
Hakumäki
Juhana M
JM
National Bio-NMR Facility, AI Virtanen Institute for Molecular Sciences, University Hospital of Kuopio, FIN-70211 Kuopio, Finland.
Gröhn
Olli H J
OH
Tyynelä
Kristiina
K
Valonen
Piia
P
Ylä-Herttuala
Seppo
S
Kauppinen
Risto A
RA
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D006561:Herpes Simplex / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D051381:Rats; D012399:Rotation; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir