Radiation dose factors for alpha -emitters in osteons and some considerations on dose non-uniformity ratios and relative distribution factors

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A biokinetic model of the systemic distribution of americium in the beagle dog is presented. The model is based on a previous biokinetic model of plutonium. The data sets used for the development of the model were the measurements of excreted activity (urine and feces) and organ burdens (skeleton, liver, and other soft tissues) for different levels of initial injected activity. In developing the model, the compartmental structure of the skeleton of the plutonium model was adopted, and only the numerical values of parameters were adapted. The model well describes the fractions of americium in the skeleton, liver, and soft tissues and the total fraction excreted in urine and feces. The tuning of the liver clearance parameter provides a realistic description of the change in the partitioning between liver and skeleton for different injection levels. The most significant features of the biokinetics and dosimetry of americium and plutonium in beagles are compared. The total fractions of the clearance to the skeleton and the liver are roughly equal to the value for plutonium, but the partitioning of americium between these organs is reversed with respect to the partitioning of plutonium. 241Am doses to liver and skeleton are similar to 239Pu doses, owing to some counteracting factors. For the highest injection level, the liver mass is dependent on the time post injection. For the skeletal tissues, the dose to the cortical endosteum by far exceeds the dose to the trabecular endosteum and the red marrow. The model provides the basis for statistical survival analyses and risk estimates.

Section: Dosimetrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Americium in the Beagle Dog: Biokinetic and Dosimetric Model

Luciani¹,

Polig²,

Lloyd³

et al. 2006

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Biokinetic and Dosimetric Model of Plutonium in the Dog

Polig¹,

Bruenger²,

Lloyd³

et al. 2000

A biokinetic model of the systemic distribution and dosimetry of 239Pu in the beagle dog is presented. To achieve maximum consistency with experimental data, known histomorphometric parameters and results of autoradiographic studies were adopted directly. The remaining parameters were determined from retention and excretion measurements by optimization procedures. The beagle model attempts to parallel the human model as much as possible, but only one liver compartment and one compartment representing other soft tissues were needed to describe the data adequately. The salient features and differences of the biokinetic behavior of 239Pu beagles and humans are compared. Generally the organ retention of the beagle in relation to the lifetime is longer than in humans. This is particularly pronounced in the skeleton. Trabecular deposits of plutonium are gradually shifted to cortical sites. For the dosimetric model some additional features disregarded in the human model were employed. These relate to bone volume labels, a gradation of concentrations in marrow, the energy-dependence of absorbed fractions, and the self-absorption in marrow. The model predicts that the contribution of surface deposits to the endosteal dose still exceeds the contributions from bone volume and marrow labels. The average endosteal dose is about eight times and the marrow dose about two times larger than the average skeletal dose. The model provides the basis for the analysis of survival and relative risks.

Effective Thresholds for Induction of Skeletal Malignancies by Radionuclides

Lloyd¹,

Taylor²,

Fisher

et al. 2000

Our analysis of data from the beagle project completed at the University of Utah has provided some comparisons that appear to be useful in testing the model proposed by Raabe of effective thresholds for induction of skeletal malignancy by bone-seeking radionuclides in beagles. Raabe's model predicted that cumulative skeletal doses of less than about 0.9 to 1.4 Gy from alpha emitters or 28 to 70 Gy from beta emitters deposited in the skeleton require a long enough time for bone cancer expression that the dog's natural lifespan would be exceeded before the tumor appeared. Results from the Utah beagle project seem to confirm these projections for 226Ra, 228Ra and, perhaps, for 90Sr. The lowest doses at which malignant bone tumors were observed in animals injected with these radium isotopes were about 0.9 Gy (226Ra) and 3 Gy (228Ra). For the beta emitter, 90Sr, the lowest doses at which bone tumors were seen were about 18, 50, and 70 Gy with an expectation for naturally occurring tumor of about one. Twenty-six of the two hundred and thirty-three Utah beagles given monomeric 239Pu that developed skeletal malignancies had doses between 0.02 and 0.51 Gy (80 of these dogs had skeletal doses of less than 0.9 Gy). Three dogs of 54 given 241Am with doses lower than 0.9 Gy had bone tumors at 0.23, 0.56, and 0.88 Gy with the expectation of about one naturally occurring case. For 25 animals injected with 228Th at skeletal doses below 0.9 Gy, one bone tumor dog had a dose of about 0.4 Gy, and the expectation of a dog with natural tumor among the group was only about 0.38. Five beagles of 74 given 224Ra with resulting doses of less than 0.9 Gy died with skeletal malignancy at 0.32 Gy or less with an expectation for non 224Ra induced tumor of about one. It appears that Raabe's proposal might be confirmed for some but not all of the radionuclides used in the Utah studies. Models presented in earlier papers by Raabe provide results that are somewhat different from his recent abstract and compare more favorably with those cited herein for Utah dogs. Re-examination of our data for these analyses has suggested a novel concept for calculation of carcinogenic dose to endosteal bone surfaces.