Purpose: Experimental in vivo radiotherapy frequently aims at the imitation of clinically applied fractionation schedules. However, the reliability of the anesthetic procedure and limited access to the treatment machines in clinical departments are major factors complicating the practical realisation of the experiment. Therefore, a reliable and time saving system for irradiations of xenografted tumors has been developed, which allows repeated irradiations, even in relatively short intervals available for experimental irradiations.
Material and methods: The system presented here consists of an acrylic distributor for an anesthetic gas mixture employing enflurane (Ethrane) in the center of the set-up. Ten mice are positioned radially around the midpoint of the set-up so that they can be irradiated simultaneously. The xenotransplanted tumors growing on the right hind leg of mice are placed in a predefined position, which was found to be of advantage in order to position the tumors for fractionated treatments in identical setting. Tumor-bearing mice are irradiated with 15 MeV photons generated by a linear accelerator at a dose rate of 2.5 Gy/min. One of the significant feature of the setup is the ability to irradiate in acute hypoxia which is obtained by use of an integrated tourniquet. The dose modifying effects of different gases can be investigated by simply using them as carrier for the enflurane.
Results: With the use of the set-up several different experiments were performed so far. At most ten fractions were given, one fraction per day. Even after these repeated treatment the loss of animals due to narcosis was less than 2%. The dose variation within the treatment field was found to be less than 4% as measured with TLD dosimetry. The remaining body of the mice is shielded effectively from the direct beam as the whole body dose of mice is 8% of the total tumor absorbed dose. The efficacy of the tourniquet technique for acute hypoxic irradiations was illustrated with the use of 99mTc-labelled albumin showing a complete stop of blood flow in the clamped leg. The steep dose-response curve obtained for single dose irradiation of a neurogenic sarcoma is based on the physical and experimental precision which can be reached with the technique suggested here.
Conclusion: Due to the high dose rate and the possibility to irradiate ten animals simultaneously the set-up introduced here is greatly time saving. The versatile applicability makes the new set-up a valuable tool for tumor radiobiology.