Abstract
Targeted alpha therapy (TAT) has the advantage of delivering therapeutic doses to individual cancer cells while reducing the dose to normal tissues. TAT applications relate to hematologic malignancies and now extend to solid tumors. Results from several clinical trials have shown efficacy with limited toxicity. However, the dosimetry for the labeled alpha particle is challenging because of the heterogeneous antigen expression among cancer cells and the nature of short-range, high-LET alpha radiation. This paper demonstrates that it is inappropriate to investigate the therapeutic efficacy of TAT by macrodosimetry. The objective of this work is to review the microdosimetry of TAT as a function of the cell geometry, source-target configuration, cell sensitivity, and biological factors. A detailed knowledge of each of these parameters is required for accurate microdosimetric calculations.
Highlights
Targeted alpha therapy (TAT) can provide selective systemic radiotherapy to primary and metastatic tumors [1]
The relative biological effect (RBE) of alpha particles is from 3 to 7 [5], which means that for the same absorbed dose, the acute biological effects of alpha particles are 3 to 7 times greater than the damage caused by external beam photons or beta radiation
Microdosimetry is concerned with the same concept of energy deposition per unit mass as dosimetry, the difference in the length of alpha particle and small size of the target volume introduces stochastic effects which are negligible in conventional dosimetry [20]
Summary
Targeted alpha therapy (TAT) can provide selective systemic radiotherapy to primary and metastatic tumors (even at a low dose rate and hypoxia region) [1]. It permits sensitive discrimination between target and normal tissue, resulting in fewer toxic side effects than most conventional chemotherapeutic drugs. Targeted cancer cells are killed by the short-range alpha radiation, while sparing distant normal tissue cells, giving the minimal toxicity to normal tissue [2]. Depletion of oxygen and nutrition, is the likely cause of cancer cell death and tumor regression [8, 9]
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