Tumor hypoxia is a well known therapeutic problem which contributes to radioresistance and aggressive
tumor characteristics. Lack of techniques for repeated measurements of
tumor oxygenation (pO(2), partial pressure of
oxygen) has restricted the optimization of
hypoxia modifying methods and their efficacious application with
radiotherapy. We have investigated a non-invasive method to enhance tissue pO(2) of peripheral
tumors using topical application of formulations with BN (
Benzyl Nicotinate), a
vasodilator, and have used EPR (Electron Paramagnetic Resonance) oximetry to follow its effect on
tumor oxygenation.We incorporated 2.5% BN in both
hydrogel and microemulsions and investigated the effects on pO(2) of subcutaneous RIF-1 (Radiation Induced
Fibrosarcoma)
tumors in C3H mice. The experiments were repeated for five consecutive days. The topical application of BN in
hydrogel led to a significant increase from a pre-treatment pO(2) of 9.3 mmHg to 11 - 16 mmHg at 30 - 50 min on day 1. However, the magnitude and the time of significant increase in pO(2) decreased with repeated topical applications. The BN in a microemulsion resulted in a significant increase from a baseline pO(2) of 8.8 mmHg to 13 - 18 mmHg
at 10 - 50 min on day 1. Experiments repeated on subsequent days showed a decline in the magnitude of pO(2) increase on repeated applications. No significant change in
tumor pO(2) was observed in experiments with formulations without BN (vehicle only).EPR oximetry was successfully used to follow the temporal changes in
tumor pO(2) during repeated applications for five consecutive days. This approach can be potentially used to enhance radiotherapeutic outcome by scheduling radiation doses when an increase in
tumor pO(2) is observed after topical applications of BN formulations.