Radionuclide therapy (RNT) uses systemically administered radiopharmaceuticals directed to a specific cancer associated target to provide low dose rate (LDR) treatment. The radiation dose is delivered to the tumor cells by continuous, but declining, exposure that is a function of the initial uptake and the variable half-life. The average dose rate for RNT is typically of the order of 2–8 Gy/day, and the maximum absorbed dose may be up to 50 Gy delivered over a period of many days. This is in marked contrast to the situation with External Beam Ratiotherapy (EBRT), where the dose is delivered at a high dose rate (HDR), typically 1–5 Gy/min, and also in contradistinction to the dose rate at which brachytherapy is delivered, typically 1–5 Gy/h. The mechanisms by which cells respond to LDR exposures are fundamentally different from those occurring at HDR. LDR exposures tend to promote loss of clonogenic potential in some cell types (e.g., lymphomas) by activating apoptotic responses, whereas high doses tend to cause necrosis as their primary mechanism of cytotoxicity. The ability to induce apoptosis varies inversely with dose rate. Many cell types exhibit an initial hypersensitive response at doses below ~25 cGy followed by a region of increasing radioresistance up to ~50 cGy. This phenomenon probably involves an alteration in the cellular processing of DNA damage as a function of dose. Radiation damage to cells is due primarily to indirect effects such as formation of free radicals in water (with their diffusion and subsequent interaction with cellular components, mostly DNA), and to some degree direct damage to DNA. Different tissues and different individuals have different abilities to respond to and repair this damage. The value of LDR therapy with radionuclides in patients with differentiated thyroid carcinoma, somatostatin receptor expressing tumors, neuroendocrine tumors, lymphoma, liver tumors, and treatment of metastatic bone pain is discussed.
- DNA damage and radiation dose
- Radiation dosimetry
- Radionuclide therapy
- Therapeutic radiopharmaceuticals
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