Radiation Dose Does Matter: Mechanistic Insights into DNA Damage and Repair Support the Linear No-Threshold Model of Low-Dose Radiation Health Risks

Abstract

1014 Objectives: Human internal dosimetry of new radiopharmaceuticals should have presumed by the animal data. Cu-64 labeled radiopharmaceuticals has possibly can use PET imaging and therapeutic effect assuming of convergence radiopharmaceutical. The aim of this study has evaluated the Cu-64 labeled radiopharmaceutical projected human internal dosimetry using small animal biodistribution and image data. Methods: Cu-64 labeled radiopharmaceutical PET image was acquired using small animal PET/CT system (Inveon, Siemens Healthcare.) in mouse (n = 3) at 1, 2, 6, 24, 48 and 72 hour after intravenous injection of Cu-64 labeled radiopharmaceutical. Each organ region was defined by contrast mouse CT image (Exitron nano 12000, Miltenyi Biotec). In this study, three internal dosimetry method which are animal derived, human extrapolated, and object specific dosimetry. Animal derived dosimetry method was estimated by estimated biodistribution in mouse and human S-value. Human extrapolate dosimetry method was calculated extrapolated human biodistribution and human S-value. Object specific dosimetry method was calculated using image based residence time and object specific S-value. Object specific S-value was calculated based on individual small animal CT image using Monte Carlo simulation. Results: Animal derived absorbed dose in heart, lung, liver, spleen were 0.048 ± 0.006, 0.028 ± 0.012, 0.079 ± 0.002, 0.047 ± 0.005 mGy/MBq, respectively. Human extrapolated absorbed dose were 0.054 ± 0.007 for heart, 0.102 ± 0.017 for lung, 0.118 ± 0.012 for liver, and 0.100 ± 0.013 mGy/MBq for spleen. Object specific absorbed dose were 0.053 ± 0.006 for heart, 0.027 ± 0.005 for lung, 0.035 ± 0.005 for liver, 0.025 ± 0.003 mGy/MBq for spleen. According to the absorbed dose, extrapolate dosimetry method has more higher estimated Cu-64 absorbed dose in lung, liver, spleen region than animal derived and object specific dosimetry Methods: Conclusion: We evaluated the human projected internal dosimetry using Cu-64 small animal data. Human extrapolated dose was overestimated in lung, liver, and spleen. Object specific dosimetry will be applied for diagnostic and therapeutic human dose calculation.