Biomarker distribution after injection into the canine prostate: implications for gene therapy

Abstract

Objective To evaluate the distribution of biomarkers after transrectal injection into the canine prostate and to report a method for enhancing the distribution of gene expression. Materials and methods Carbon black was first used to evaluate the histopathological distribution in canine prostate of single or multiple injections via the transurethral, transperineal and transrectal routes. The distribution of canarypox virus (ALVAC) vector‐delivered gene expression was then compared using both fluid‐phase injection techniques and delivery in a solid carrier composed of a gelatine sponge matrix. Results After transurethral administration, carbon black was detected as scattered particles in ducts and acini, mostly in the periphery of the gland. Direct transrectal injection of carbon black resulted in a localized collection at the site of injection, with only a minimal peri‐acinar distribution. Transrectal injection of the fluid‐phase (virus suspended in diluent) ALVAC vector encoding the β‐galactosidase gene resulted in a similar distribution, with limited gene expression at the site of injection and in the needle track. Delivery of the same number of virus particles in the gelatine sponge matrix resulted in qualitatively greater gene expression. Conclusions Direct injection of the canine prostate with biomarkers, including viral vectors, in the fluid‐phase results in very localized gene expression, while the distribution was more widespread after delivery in a gelatine sponge matrix.

TNF-related apoptosis-inducing ligand (TRAIL): A new path to anti-cancer therapies

“…Numerous substances have been used as carriers to enhance and sustain the delivery of soluble products to cancerous and normal tissues (Lee et al, 1997; Machan et al, 1997). One such agent is Gelfoam (Pfizer, Kalamazoo, MI), a collagen-based matrix that enhances the distribution and expression of virally-delivered genes when injected intratumorally (Siemens et al, 2000a; Siemens et al, 2000b). Gelfoam is able to absorb and hold within its interstices ~45 times its weight of blood and other fluids (Chemistry, 1947), and the absorptive capacity of Gelfoam is a function of its physical size, increasing with increasing gelatin volume (Goodman and Gliman, 1980).…”