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 (7.3 × 10⁴ ± 2 × 10⁴ photons/ sec/cm²/steradian (p/sec/cm²/sr) on day 4 and 7.0 × 10⁴ ± 4 × 10⁴ p/sec/cm²/sr on day 21). Low levels of transduction were also observed in the spleen and liver (5.0 × 10² ± 1.7 × 10² 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.