| Distribution, retention, and excretion of intramuscularly injected 241Am citrate have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay and retention data, obtained from experiments done by Patricia Durbin and her colleagues at Lawrence Berkeley National Laboratory, were evaluated against the International Commission on Radiological Protection (ICRP 67) 241Am systemic model coupled with to the National Council on Radiation Protection and Measurement wound model (NCRP 156). The default transfer rates suggested in these models were used with the urine and feces excretion data to predict the intake as well as liver and skeleton tissue contents at the time of death. The default models produced adequate fits using urine bioassay data, but the injected activities were over-predicted by as much as 4.41 times and under-predicted by as much as 0.99 times. Poor prediction has been observed in all cases using fecal excretion. The retained activity in the liver and skeleton at the time of death were investigated using the same approach. It appears that the models accurately predict the amount of the activity retention in the skeleton more accurately than in the liver. A practical decision was established whereby the ICRP 67 and NCRP 156 parameters predicted the skeleton retention within 20% of the measured values. The fraction of predicted to measured activity at the time of death in the skeleton was over 1.0 in most cases and accurate predictions were obtained in 7 cases. The predicted activity in skeleton for these cases ranged from 14% under the known value to 17% over. NHPs’ urine data and organ retention were compared with data from previously modeled baboons and beagle dogs. About six percent of the injected activity in NHP was excreted in urine and approximately 0.1% in feces in the first 24h. The results from NHP is different from excreta analysis in baboons and beagle dogs. Urinary excretion in the cynomolgus, rhesus, and baboon NHPs is the dominate pathway of Am-214 clearance, however, the fecal excretion are considered dominate by the end of second week in baboons and the end of the third week in NHPs. Urinary excretion is considered the dominate pathway of clearance in beagle dogs until the end of the experiment. The comparison between NHP and human is difficult due to the differences in the amount of activity translocated or deposited in the liver tissue and non-liver tissues (primarily skeleton), in addition; to the physiological differences between the NHP and human. Another objective of this study was to develop new transfer rate parameters for wound and systemic models in an effort to improve the biokinetic predictions. Estimates of new transfer rates appropriate for the nonhuman primate data were determined by employing a companion program called IMBAUA. During validation of the suggested transfer rates, it was observed that the optimized parameters predicted the intake in 66% of the tested animals used in this investigation. The activity retained in the skeleton improved in almost all cases where the differences between the predicted and measured activity in a value less than 20%. However, the modified parameters did not improve the fit in three cases where the ratio of observed to predicted values of the were less than 0.05. (Work performed with partial support from funding from the National Institute of Allergy and Infectious Diseases under contract HHSN272201000046C). |