Changes in the tumor microenvironment during low-dose-rate permanent seed implantation iodine-125 brachytherapy

Purpose: There is a lack of data regarding how the tumor microenvironment (e.g., perfusion and oxygen partial pressure [pO(2)]) changes in response to low-dose-rate (LDR) brachytherapy. This may be why some clinical issues remain unresolved, such as the appropriate use of adjuvant external beam radiation therapy (EBRT). The purpose of this work was to obtain some basic preclinical data on how the tumor microenvironment evolves in response to LDR brachytherapy. Methods and Materials: In an experimental mouse tumor, pO(2) (measured by electron paramagnetic resonance) and perfusion (measured by dynamic contrast-enhanced magnetic resonance imaging) were monitored as a function of time (0-6 days) and distance (0-2 mm and 2-4 mm) from an implanted 0.5 mCi iodine-125 brachytherapy seed. Results: For most of the experiments, including controls, tumors remained hypoxic at all times. At distances of 2-4 mm from radioactive seeds (similar to 1.5 Gy/day), however, there was an early, significant increase in pO(2) within 24 h. The pO(2) in that region remained elevated through Day 3. Additionally, the perfusion in that region was significantly higher than for controls starting at Day 3. Conclusions: It may be advantageous to give adjuvant EBRT shortly (similar to 1 to 2 days) after commencement of clinical LDR brachytherapy, when the pO(2) in the spatial regions between seeds should be elevated. If chemotherapy is given adjuvantly, it may best be administered just a little later (similar to 3 or 4 days) after the start of LDR brachytherapy, when perfusion should be elevated. (c) 2005 Elsevier Inc.