title: Radiation dose to abdominal organs of the mouse due to 90Y in the urinary bladder.
abstract: Radiation dosimetry estimates in mice have proven useful in evaluating therapeutic radiopharmaceuticals. Current models for mice do not take into account the dose to abdominal organs from radioactivity in the urinary bladder. Although the dose from this source is probably low for slowly clearing compounds such as antibodies, it may be considerable for small molecule (90)Y conjugates undergoing rapid renal clearance. To evaluate this possibility, we modeled the mouse bladder as a 6 mm sphere, surrounded by a 0.5 mm thick shell. We then calculated the radiation dose that might be received by the shell and by more distant points, using the point kernel method with the Loevinger analytical point kernel. A Monte Carlo calculation using EGS4 was also performed. Surface dose calculations were compared with in vitro experimental data. LiF TLD dosimeters were placed directly under five separated, flat-bottomed, 6-mm diameter wells containing (90)Y on a 96-well plate. Dose versus distance from the mouse urinary bladder was calculated using kinetic data from imaging studies of a renally cleared (111)In analog compound currently under investigation. From this, it was estimated that whole body administration of 34.8 MBq of the (90)Y analog compound would yield a bladder wall dose estimate of approximately 98 Gy. Structures within 2 mm of the bladder would receive additional estimated doses of at least 15 Gy. This radiation dose approaches that which is known from external beam data to cause fibrosis in mice. Because of the greater size of the human bladder compared with that of the mouse relative to the range of (90)Y beta particles, the radiation exposure from the same residence time in man was estimated to be considerably lower. This highlights a potential practical limitation of extrapolating radiotoxicity findings in the mouse to human subjects.
authors.affiliation: Bristol-Myers Squibb Medical Imaging, N. Billerica Massachusetts 01862, USA. joel.lazewatsky@bms.com
authors.forename: Joel
authors.initials: J
authors.lastname: Lazewatsky
authors.forename: Yihong
authors.initials: Y
authors.lastname: Ding
authors.forename: David
authors.initials: D
authors.lastname: Onthank
authors.forename: Paula
authors.initials: P
authors.lastname: Silva
authors.forename: Eric
authors.initials: E
authors.lastname: Solon
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
mesh_terms: D000005:Abdomen / Q000528:radiation effects*; D000818:Animals; D005260:Female; D039302:Integrin alphaVbeta3 / Q000528:radiation effects*; D008297:Male; D051379:Mice; D009010:Monte Carlo Method; D011829:Radiation Dosage; D001743:Urinary Bladder / Q000528:radiation effects*; D015021:Yttrium Radioisotopes / Q000008:administration & dosage*
chemical_list: D039302:Integrin alphaVbeta3; D015021:Yttrium Radioisotopes