Stereotactic radiosurgery of the rat dunning R3327-AT1 prostate tumor.

Stereotactic radiosurgery (RS) is being used increasingly for the treatment of small benign and malignant lesions, particularly in the brain. However, to fully realize the potential of this technique, more experimental data are needed. In this report we describe an RS technique suitable for small animals, and present the results obtained with different irradiation doses and volumes given to a rat prostate tumor. Single doses of RS were administered to the Dunning prostate R3327-AT1 carcinoma transplanted subcutaneously into the thigh of male Copenhagen rats. The tumors (approximately 5 mm in diameter) were localized within a stereotactic frame and irradiated at a linac facility (15 MV) with single doses of 15.3, 30.6, 46.0, 61.3, or 76.6 Gy at the 80% isodose level using narrow beams from 3- and 5-mm collimators (80% isodose field size of 5 or 8.5 mm, respectively) and a six-arc irradiation technique. Tumor size was measured three times a week (Mondays, Wednesdays, and Fridays). Conventional stains were used to examine the histologic status of the tumors. To evaluate the proliferative response of the tumors to RS and assess the prevalence and spatial distribution of proliferating cells, tissue slices were stained with the proliferation markers 5-bromo-2'- deoxyuridine and proliferating cell nuclear antigen 4 and 8 h, and 4, 8, 12, and 210 days after stereotactic irradiation with a dose of 61.3 Gy. The extent of growth delay and local tumor control depended on the radiation dose, the field size, and the accuracy of irradiation. Local control at day 100 ranged from two of eight rats at 30.6 Gy, five of seven rats at 61.3 Gy, and six of seven at 76.6 Gy. No overt side effects in the surrounding tissues was observed. After 61.3 Gy, the immunohistochemical staining revealed a rapid decrease of proliferative active tumor cells after irradiation. The irradiated tumor tissue was gradually replaced by connective tissue. However, in one persistent nodule, a few proliferative cells were detected even after 200 days. A radiosurgical technique was successfully developed for a small animal system. The technique was concluded to be reproducible and suitable for future use in single and fractionated treatment regimens.