TAT - Radiation Physics

These aspects range from the radiation safety during handling of various radioactive sources, calculation of microdosimetric properties regarding irradiation of single cells, dosimetry and the determination of the absorbed dose to tumors, bone marrow or other normal tissues, estimate of the relative biological effectiveness (RBE) for various end-points, estimation of the maximum tolerated absorbed dose or activity for various treatment situations, and considerations regarding tumor cure probability for different treatments and therefore irradiation situations.

In the work in J Nucl Med 2006;47:1342–1350 calculations were done in order to estimate the absorbed dose to differently sized tumors. 

Some examples of studies in which different aspects of radiation physics have been considered are presented below.

In the work in Med Phys 2004;31:218-225 a microdosimetric analysis of ²¹¹At irradiation of cancer cells was done. A custom-built computer program based on the Monte Carlo method was used to simulate the irradiation. The results show that ²¹¹Po atoms, created on a cell surface by the decay of ²¹¹At atoms, will diffuse from the cell during its life-span. The increasing distance to the cell nucleus will drastically decrease the probability of the emitted alpha particle to hit the cell nucleus. The conclusion was that for dispersed cells, the diffusion of ²¹¹Po atoms will reduce the total absorbed dose from cell-bound ²¹¹At by a factor of 2.

In the work in J Nucl Med 2005;46:464–471 the myelotoxicity and the RBE for alpha-particles emitted from ²¹¹At was investigated in a pre-clinical study. An RBE of 3.4 ± 0.6 and 5.0 ± 0.9 was found when comparison was made with electrons emitted from ^99mTc or generated by gamma rays emitted from an external ⁶⁰Co source. The end-point parameter was degree of myelosuppression.

Finally, in the work in J Nucl Med 2005;46:2061–2067 the aim was to evaluate the RBE of ²¹¹At compared with that of ⁶⁰Co gamma-irradiation. The endpoint was growth inhibition (GI) of subcutaneous xenografts. The Balb/c received an intravenous injection of ²¹¹At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of ²¹¹At in tumors and organs at different times after injection. External irradiation of the tumors was performed with ⁶⁰Co. The biodistribution study showed the uptake of the immunoconjugates by the tumor to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of ²¹¹At corresponded to absorbed doses in tumors of 1.35, 2.65, and 3.70 Gy. The value (mean ± SEM) for D37 was 1.59 ± 0.08 Gy. Tumor growth after ⁶⁰Co external irradiation showed a value for D37 of 7.65 ± 1.0 Gy. The corresponding RBE of ²¹¹At irradiation was 4.8 ± 0.7.