The role of time-factor and RBE for the induction of osteosarcomas by incorporated short-lived bone-seekers.

In a large series of experiments, fractionated injections of short-lived bone-seekers have been shown in many cases to cause a remarkable increase of the osteosarcoma incidence compared with a single administration of the same total skeletal dose. This effect has been observed with both alpha- and beta-emitters. In addition the latency period was shortened by protracting the dose. The total skeletal doses investigated ranged between 0.9 and 20 Gy for alpha-emitters (224Ra and 227Th) and between 28 and 112 Gy for the beta-emitter (177Lu). In all cases the protracted dose had higher or at least equal effects when compared with a single application. Reference experiments with long-lived alpha- and beta-emitting bone-seeking nuclides (226Ra and 90Sr) showed that the incidence of osteosarcomas per Gy was sometimes lower than that observed when the same skeletal dose was applied by protraction of short-lived radionuclides. The dependence of osteosarcoma incidence on dose-time distribution, duration of internal irradiation, and radiation quality is discussed. In this context the possibility that the critical initial dose rate may be related to the initiating event within the multi-stage hypothesis of carcinogenesis is considered.