Effects of rate, volume, and dose of intratumoral infusion on virus dissemination in local gene delivery

Abstract

Recent studies have shown that up to 90% of viral vectors could disseminate to normal organs following intratumoral infusion. The amount of dissemination might be dependent on the infusion conditions. Therefore, we investigated the effects of infusion rate, volume, and dose on transgene expression in liver and tumor tissues after intratumoral infusion of an adenoviral vector encoding luciferase. Luciferase expression was determined through bioluminescence intensity measurement. We observed that the luciferase expression in the liver was independent of the infusion rate but increased with the infusion dose, whereas the luciferase expression in the tumor was a bell-shaped function of the infusion rate. The latter observation was consistent with the distribution pattern of Evans blue -labeled albumin after its solution was infused into tumors at the same infusion rates. We also observed that the infusion volume could affect luciferase expression in the tumor but not in the liver. These observations implied that virus dissemination was determined mainly by the infusion dose, whereas the amount of transgene expression in the tumor depended on the distribution volume of viral vectors in the tumor as well as the infusion dose. [Mol Cancer Ther 2006;5(2):362 -6]

Adenoviral Gene Delivery to Solid Tumors by Recombinant Silk–Elastinlike Protein Polymers

“…Intratumoral infusion can bypass the initial filtering events in normal tissues and facilitate virus transport in tumors (6). However, a potential problem in this approach is that most of the viral vectors disseminate from tumor to normal tissues during and after infusion (8). The concentration of transgene products in normal organs such as liver, may still exceed normal tissue tolerance if the products are highly toxic (10).…”

Factors influencing retention of adenovirus within tumours following direct intratumoural injection

“…[11][12][13][14][15] Dissemination into the circulation following IT injection has already been reported in both animal studies and clinical trials. [16][17][18] For example Wang et al (2006) 19 explored injecting 20 or 50 ml of adenovirus solution IT, using an infusion rate of 1.0 ml s À1 . With all injectate volumes there was considerable hepatic transduction, particularly at higher virus doses, implying shedding of viable virus from the tumour into the circulation although virus particle kinetics were not measured directly.…”

Numerical study of nanofluid infusion in deformable tissues for hyperthermia cancer treatments

“…Since most of the ferrofluids used in the experimental study of magnetic nanoparticle hyperthermia have a low concentration [30,31,35], we assume that the nanofluids used in a treatment are dilute with a concentration lower than 5% by volume, where the presence of the particles does not significantly affect the transport properties of the fluid [36]. We also assume that the porous structure before an injection is homogenous.…”

“…The infusion rate in real tumors reported in Ref. [35] varies in the range of 1.5-30 ll min -1 . Since our study focuses on the nanofluid transport in tumors, we choose infusion rates in the range of 5 -20 ll min -1 in this study.…”