title: Bioluminescence imaging of systemic tumor targeting using a prostate-specific lentiviral vector.
abstract: Developments in vector design using tissue-specific and tumor-specific promoters have led to significant improvements in tumor-targeting strategies. These developments combined with the ability to monitor gene expression by molecular imaging have facilitated the detection and prolonged monitoring of disease progression in small-animal models. Bioluminescence imaging offers a convenient and sensitive platform for monitoring gene expression patterns in preclinical models of gene therapy. Targeting a specific subset of cells/tissues via systemic delivery of vectors would be highly beneficial in gene therapy protocols. Using a two-step transcriptional amplification (TSTA)-based lentiviral vector (LV-TSTA), we demonstrate specific targeting of prostate tumors in vivo after systemic administration of lentivirus. Four days after intravenous administration of LV-TSTA into adult severe combined immunodeficient (SCID) mice (n=5) carrying subcutaneous prostate tumors, we found significant levels of transduction at the tumor site when compared with other organs (p<0.05). Gene expression was sustained in the tumor for up to 3 weeks (7.3x10(4)+/-2x10(4) photons/ sec/cm2/steradian (p/sec/cm2/sr) on day 4 and 7.0x10(4)+/-4x10(4) p/sec/cm2/sr on day 21). Low levels of transduction were also observed in the spleen and liver (5.0x10(2)+/-1.7x10(2) p/sec/cm2/sr). The results from this study support the use of TSTA-based lentiviral vectors for prostate tumor targeting after systemic delivery. Noninvasive imaging using such vectors should be useful for monitoring long-term gene expression in gene therapy applications.
authors.affiliation: Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095-1770, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Iyer
authors.forename: Felix B
authors.initials: FB
authors.lastname: Salazar
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Carey
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D023061:Gene Order / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D008099:Liver / Q000737:chemistry; D049409:Luciferases, Firefly / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000628:therapy*; D013154:Spleen / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D049409:Luciferases, Firefly