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

Abstract

There is a lack of data regarding how the tumor microenvironment (e.g., perfusion and oxygen partial pressure [pO2]) 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. In an experimental mouse tumor, pO2 (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. For most of the experiments, including controls, tumors remained hypoxic at all times. At distances of 2-4 mm from radioactive seeds ( approximately 1.5 Gy/day), however, there was an early, significant increase in pO2 within 24 h. The pO2 in that region remained elevated through Day 3. Additionally, the perfusion in that region was significantly higher than for controls starting at Day 3. It may be advantageous to give adjuvant EBRT shortly (approximately 1 to 2 days) after commencement of clinical LDR brachytherapy, when the pO2 in the spatial regions between seeds should be elevated. If chemotherapy is given adjuvantly, it may best be administered just a little later (approximately 3 or 4 days) after the start of LDR brachytherapy, when perfusion should be elevated.