Reproducibility of neutron activated Sm-153 in tablets intended for human volunteer studies

摘要

Neutron activation of non-radioactive Sm-152 to Sm-153 offers a valuable method of radiolabeling for the in vivo study of the behavior of oral dosage formulations. In particular this methodology allows the manufacture of a pharmaceutical formulation without the need for radioactive laboratory facilities. During manufacturing a small amount of Sm-152 is added to the formulation. This is then irradiated with neutrons to produce the Sm-153 that can be used for in vivo imaging of formulation transit and release using a standard gamma camera. Prior to clinical investigation it is essential to validate the manufacturing procedure to ensure that the activated material is within accepted limits. In particular the amount of radioactivity administered should be within a specified tolerance level. This will be required as part of the condition of ethical approval for human study. The final activity produced and hence the radiation effective dose to patients or healthy subjects is dependent on a number of factors including the amount of incorporated Sm_2O_3 (mg), the reactor neutron flux (cm~V) and the irradiation period (s). We have investigated the reproducibility of the activated activity as part of the validation process for in vivo clinical studies. 96 placebo tablets each containing 10 mg of Sm_2O_3 were irradiated using a thermal neutron flux of 5 x 10~(12) cn~(-2)s~(-1) for 70 s to achieve the radioactivity of 1 MBq at the time of administration. This corresponded to 0.8 mSv effective dose per administration. The tablets were assayed prior to the administration to the volunteer subjects using the radionuclide assay calibrator. The range of activities obtained prior to dosing was 0.82 - 0.95 MBq (mean ± SD: 0.887 ± 0.026). This was considered acceptable since it was below the 1 MBq Dose Reference Level and within the permitted radiation dose granted by the ethical study review. This study demonstrates the factors affecting the activity produced by neutron activation of oral formulations containing Sm-152 and the data confirm the reproducibility of the activity produced over an extended period of 10 weeks.