Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment

Abstract

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of 131I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the 131I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on 131I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO2 was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with 131I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8+/-3.60 in the nontreated controls, 13.9+/-2.17 with PTX, 3.43+/-0.44 with RIT, and 1.86+/-0.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of 131I-A7. However, intratumoural pO2 was significantly improved by PTX administration: 16.9+/-9.75 mmHg in control tumours versus 25.6+/-11.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.