Tumour control probability (TCP) for non-uniform activity distribution in radionuclide therapy

Non-uniform radionuclide distribution in tumours will lead to a non-uniform absorbed dose. The aim of this study was to investigate how tumour control probability (TCP) depends on the radionuclide distribution in the tumour, both macroscopically and at the subcellular level. The absorbed dose in the cell nuclei of tumours was calculated for (90)Y, (177)Lu, (103m)Rh and (211)At. The radionuclides were uniformly distributed within the subcellular compartment and they were uniformly, normally or log-normally distributed among the cells in the tumour. When all cells contain the same amount of activity, the cumulated activities required for TCP = 0.99 ((approximate)A(TCP=0.99)) were 1.5-2 and 2-3 times higher when the activity was distributed on the cell membrane compared to in the cell nucleus for (103m)Rh and (211)At, respectively. TCP for (90)Y was not affected by different radionuclide distributions, whereas for (177)Lu, it was slightly affected when the radionuclide was in the nucleus. TCP for (103m)Rh and (211)At were affected by different radionuclide distributions to a great extent when the radionuclides were in the cell nucleus and to lesser extents when the radionuclides were distributed on the cell membrane or in the cytoplasm. When the activity was distributed in the nucleus, (approximate)A(TCP=0.99) increased when the activity distribution became more heterogeneous for (103m)Rh and (211)At, and the increase was large when the activity was normally distributed compared to log-normally distributed. When the activity was distributed on the cell membrane, (approximate)A(TCP=0.99) was not affected for (103m)Rh and (211)At when the activity distribution became more heterogeneous. (approximate)A(TCP=0.99) for (90)Y and (177)Lu were not affected by different activity distributions, neither macroscopic nor subcellular.