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Targeted Alpha Therapy Essay

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Targeted Alpha Therapy (TAT) is a promising method of the targeted radio-immunotherapy for the treatment of hematologic malignancies and extended to treat various solid cancers. Alpha-Immuno-Conjugate (AIC) is the diagnostic radiopharmaceutical compound used in clinical trials of TAT. Two essential elements of AIC must be included: a targeting antigen as a carrier that tends to attach the molecules on the surface of a specific tumor cell; and an Alpha emitter that undergoes Alpha decay to kill the DNA of the targeted cell [1]. With the use of such a targeted high Linear Energy Transfer (LET) radiation therapy, highly targeted treatment to microscopic tumor cells with AIC becomes an emerging option for local and systemic cancer treatment. …show more content…

The efficacy and toxicity of TAT is closely related to the blood circulation in tumor and normal vasculature, respectively. Some AICs injected intravenously may miss the biological target and could travel by convection and diffusion along with blood or lymphatic circulation. They cause damage to the adjacent normal cells along its pathway. Furthermore, the bonding between the emitter and antigen tends to break due to the recoil energy. As a result, the emitter and its decay daughters will travel a longer distance, resulting in damage to surrounding tissues or organs.
To better understand the transient toxicity of Alpha particle to the normal cells and provide a more effective guidance for the clinical trial, a multi-physics modeling is essential to investigate this problem through the coupling of dose evaluation and hemodynamic models. Clinical trials found that conventional macro-dosimetry model cannot explain the results of some experiments [7]. Consequently, the framework of micro-dosimetry that takes into account the stochastic nature of energy deposits in mesoscale or nanoscale is essential to evaluate the dose in nucleus for Alpha particles based on the following reasons. Firstly, the high energy of Alpha particles is deposited in a short range and varies from cell to cell. This makes it very hard for a detector to measure the actual dose experimentally. Secondly, the Alpha track length is in micrometer level that

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