Feasibility of Adenovirus-Mediated hNIS Gene Transfer and 131I Radioiodine Therapy as a Definitive Treatment for Localized Prostate Cancer

摘要

We have developed a replication-competent adenovirus (Ad5-yCD/mutTKSR39rep-hNIS) armed with two suicide genes and the human sodium iodide symporter (hNIS) gene. In this context, hNIS can be used as a reporter gene in conjunction with nuclear imaging and as a potentially therapeutic gene when combined with ¹³¹I radioiodine therapy. Here, we quantified the volume and magnitude of hNIS gene expression in the human prostate following injection of a high Ad5-yCD/mutTKSR39rep-hNIS dose using a standardized injection algorithm, and estimated the radiation dose that would be delivered to the prostate had men been administered ¹³¹I with curative intent. Six men with clinically localized prostate cancer received an intraprostatic injection of Ad5-yCD/mutTKSR39rep-hNIS under transrectal ultrasound guidance. All men received 2 × 0.5 ml deposits (5 × 10¹¹ vp/deposit) in each of the four base and midgland sextants and 2 × 0.25 ml deposits (2.5 × 10¹¹ vp/deposit) in each of the two apex sextants for a total of 12 deposits (5 × 10¹² vp) in 5 ml. On multiple days after the adenovirus injection, men were administered sodium pertechnetate (Na^99mTcO4) and hNIS gene expression in the prostate was quantified by single photon emission computed tomography (SPECT). hNIS gene expression was detected in the prostate of six of six (100%) men. On average, 45% (range 18–83%) of the prostate volume was covered with gene expression. Had men been administered 200 mCi ¹³¹I, we estimate that the mean absorbed dose to the prostate would be 7.2 ± 4.8 Gy (range 2.1–13.3 Gy), well below that needed to sterilize the prostate. We discuss the obstacles that must be overcome before adenovirus-mediated hNIS gene transfer and ¹³¹I radioiodine therapy can be used as a definitive treatment for localized prostate cancer.