Abstract
Theranostic drugs under development for prostate cancer (PCa) must be tested in a large animal model prior to human clinical trials. We developed an orthotopic PCa model in dogs to target the gastrin-releasing peptide receptor (GRPR). Prostate cancer in men markedly overexpresses GRPR compared to normal or hyperplastic prostate. Canine Ace-1 PCa cells were transfected with and stably expressed the GRPr. The cells were validated by radioligand binding of 125-I-bombesin (BBN). Cells were then implanted into the prostates of immunosuppressed beagles using ultrasound guidance and allowed to grow for 4-6 weeks. To initially validate the canine model, the prostate artery was catheterized unilaterally and the BBN analog, 800-G-Abz4-t-BBN (AMBA), chelated to a near infrared fluorescent, was injected intra-arterially. Euthanasia and necropsy were performed 24-48 h later. Fluorescence in the prostate was correlated with histopathology. Histopathology confirmed that fluorescent AMBA strongly labeled multifocal tumor foci within the prostate with very little background fluorescence in normal prostate. The unilateral infusion was sufficient to label tumor on both sides of the prostate. Transfected canine Ace-1 PCa tumors grew well in vivo while maintaining the expression of GRPr. This large animal model of PCa are being used to test the specificity in vivo. Ultimately, it will be used to assess the safety and efficacy of radioactive bombesin analogs, hopefully leading to a safe, selective, and highly effective radiotherapy for human prostate cancer.
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