Berrada, M., Yang, Z. and Lehnert, S. M. Sensitization to Radiation from an Implanted ¹²⁵I Source by Sustained Intratumoral Release of Chemotherapeutic Drugs. Radiat. Res. 162, 64–70 (2004).

We have investigated tumor response to low-dose-rate irradiation from an implanted ¹²⁵I source alone or in conjunction with intratumoral drug administration. The drug (cis-DDP or 5-FU) was incorporated homogeneously into the co-polymer CPP-SA, 20:80, and the polymer/drug rods were implanted in the RIF-1 fibrosarcomas growing subcutaneously in C3H mice. Twenty-four hours later, the tumor was implanted with an ¹²⁵I seed. Tumor growth time was the end point in these experiments. For implanted ¹²⁵I sources of different dose rates and implant times giving a range of total doses, a consistent dose–response relationship was shown between tumor growth time and total dose. In other experiments, ¹²⁵I sources of different specific activities were implanted for periods of time adjusted so that the total dose to the tumor was always the same. When the ¹²⁵I implant was combined with 5-FU, greater than additive responses were seen for both short (30 h) and long (96 h) ¹²⁵I treatment times. In contrast, a short-duration (30 h) ¹²⁵I implant combined with cis-DDP was the least effective treatment, giving a combined response that was no better than additive, whereas 96 h exposure to ¹²⁵I combined with cis-DDP was the most effective combined treatment. It is conjectured that this inverse dose-rate effect seen when cis-DDP is combined with low-dose rate radiation is related to a cell cycle effect and/or to inhibition of repair of radiation damage by cis-DDP.