title: Theranostic Imaging of Cancer Gene Therapy.
abstract: Gene-directed enzyme prodrug therapy (GDEPT) is a promising therapeutic approach for treating cancers of various phenotypes. This strategy is independent of various other chemotherapeutic drugs used for treating cancers where the drugs are mainly designed to target endogenous cellular mechanisms, which are different in various cancer subtypes. In GDEPT an external enzyme, which is different from the cellular proteins, is expressed to convert the injected prodrug in to a toxic metabolite, that normally kill cancer cells express this protein. Theranostic imaging is an approach used to directly monitor the expression of these gene therapy enzymes while evaluating therapeutic effect. We recently developed a dual-GDEPT system where we combined mutant human herpes simplex thymidine kinase (HSV1sr39TK) and E. coli nitroreductase (NTR) enzyme, to improve therapeutic efficiency of cancer gene therapy by simultaneously injecting two prodrugs at a lower dose. In this approach we use two different prodrugs such as ganciclovir (GCV) and CB1954 to target two different cellular mechanisms to kill cancer cells. The developed dual GDEPT system was highly efficacious than that of either of the system used independently. In this chapter, we describe the complete protocol involved for in vitro and in vivo imaging of therapeutic cancer gene therapy evaluation.
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA, 94305, USA.
authors.forename: Thillai V
authors.initials: TV
authors.lastname: Sekar
authors.affiliation: Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA, 94305, USA. paulmur8@stanford.edu.|Department of Radiology, Stanford University School of Medicine, 3155, Porter Drive, #2236, Palo Alto, CA, 94304, USA. paulmur8@stanford.edu.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D015774:Ganciclovir; D015870:Gene Expression; D023061:Gene Order; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D000072078:Positron Emission Tomography Computed Tomography; D011355:Prodrugs / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D005456:Fluorescent Dyes; D011355:Prodrugs; D011993:Recombinant Fusion Proteins; D049409:Luciferases, Firefly; D013937:Thymidine Kinase; D015774:Ganciclovir
keywords: Bioluminescence; Firefly luciferase; Gene-directed enzyme prodrug therapy; Herpes simplex thymidine kinase; In vivo imaging