Dunning R3327-H and R3327-AT tumors growing subcutaneously in the flanks of Fischer X Copenhagen rats were irradiated with 137Cs gamma-rays at volumes of approximately 300 mm. The effects of various doses of radiation were estimated by measurements of subsequent tumor growth as well as by histological evaluation. The well-differentiated, hormonally-responsive R3327-H tumor was more radiosensitive than the anaplastic R3327-AT tumor. The reasons for this increased radiation sensitivity of the R3327-H tumor include a greater "apparent" radiation sensitivity of tumor cells and the absence of tumor hypoxia. The presence of hypoxic tumor stem cells was inferred from significant radiosensitization of tumor growth delay by 0.5 mg./gm. misonidazole and by a technique which utilizes radioactively-labelled misonidazole as a marker for hypoxic cells. The persistence of a mass of R3327-H tumor tissue after aggressive radiotherapy was not indicative of tumor cells. Furthermore, the rapid increase in volume of R3327-AT cells after aggressive radiotherapy was attributed to limited proliferation of tumor cells which were destined to ultimately die. Possible implications of these findings for the management of human prostatic adenocarcinoma are discussed.

Two prostate tumour models (Dunning R3327H and AT) were tested in rats to see if they were sensitive to hematoporphyrin-photoradiation therapy (HPD-PRT). The R3327H tumours were irradiated by implantation of a single fiber optic and the R3327 AT tumours were treated with implantation of four fiber optics simultaneously. Thermal measurements made at the tip of the fiber and up to 1 cm from the tip indicated temperature rises from 1.5 degree C to 20 degrees C at the tip and 0 degree to 8 degrees C distal to the tip, with power densities ranging from 100 mW to 500 mW. The R3327H tumour was controlled up to 8 weeks post-HPD-PRT, when the initial tumour size was 400-500 mm3. The R3327 AT tumours also respond to the HPD-PRT but a significant laser-induced thermal rise in the tumour is suspected.