Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether th is agent would enhance the response of rumours to experimental radioimmunot herapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of I-131-A7 anti-colorectal monoclonal antibody . A dose of 50 mg/kg of PTX was administered i.p. immediately after the I-1 31-A7 injection and daily thereafter for 7 days. The effect of PTX administ ration on I-131-A7 targeting in tumours was assessed with biodistribution a nd radioluminography on day 2. Intratumoural pO(2) was measured with microe lectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with I-131-A7 was significantly improved by PTX: tu mour volumes on day 15, relative to the initial volume, were 16.8 +/-3.60 i n the nontreated controls, 13.9 +/-2.17 with PTX, 3.43 +/-0.44 with RIT, an d 1.86 +/-0.59 with RIT+PTX (P <0.05). PTX administration did not alter the biodistribution or intratumoural distribution of I-131-A7. However, intrat umoural pO(2) was significantly improved by PTX administration: 16.9 +/-9.7 5 mmHg in control tumours versus 25.6 +/- 11.3 mmHg in PTX-treated tumours (P <0.01). These re suits indicate that PTX-induced radiosensitisation of t umour cells due to better oxygenation is responsible for the better RIT out comes, because the net radiation absorbed dose to the tumours did not appea r to be changed.