The Biological Effects of Radium-224 Injected into Dogs

A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected ^{224}{\rm Ra}$ chloride. The ^{224}{\rm Ra}$ chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of ^{224}{\rm Ra}$ resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of ^{224}{\rm Ra}\ {\rm kg}^{-1}$ body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected ^{224}{\rm Ra}$ (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected ^{224}{\rm Ra}$ was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed α-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of ^{224}{\rm Ra}$ and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. The occurrence of bone tumors was highest in the dogs given the highest dose in 50 injections. The age-specific incidence rate for mammary tumors was increased in all three injection groups. The results of this study revealed two important exposure-rate effects. Hematological dyscrasia was amplified by delivery of relatively high doses at a high exposure rate. In contrast, bone tumors were amplified by delivery of relatively high doses at a lower exposure rate (i.e. dose delivered over 1 year rather than 1-3 months). There was a dose-response relationship for the induction of nasal mucosal tumors and mammary tumors. These findings in dogs are similar to those in humans injected with ^{224}{\rm Ra}$, except for the