Tumor R2* is a prognostic indicator of acute radiotherapeutic response in rodent tumors.

Abstract

To test the prognostic potential of tumor R2* with respect to radiotherapeutic outcome. Blood oxygenation level dependent (BOLD) MRI images are sensitive to changes in deoxyhemoglobin concentration through the transverse MRI relaxation rate R2* of tissue water, hence the quantitative measurement of tumor R2* may be related to tissue oxygenation. Tumor growth inhibition in response to radiation was established for both GH3 prolactinomas and RIF-1 fibrosarcomas with animals breathing either air or carbogen during radiation. In a separate cohort, the baseline R2* and carbogen (95% O2, 5% CO2)-induced DeltaR2* of rat GH3 prolactinomas and murine RIF-1 fibrosarcomas were quantified using multigradient echo (MGRE) MRI prior to radiotherapy, and correlated with subsequent tumor growth inhibition in response to ionizing radiation, while the animals breathed air. A radiation dose of 15 Gy caused pronounced growth delay in both tumor models and transient regression of the GH3 prolactinomas. When the animals breathed carbogen during radiation, the growth delay/regression was enhanced only in the GH3 prolactinomas. The GH3 prolactinomas, which exhibit a relatively fast baseline R2* and large DeltaR2* in response to carbogen breathing prior to radiotherapy, showed a substantial reduction in normalized tumor volume to 66 +/- 3% with air breathing and 36 +/- 5% with carbogen seven days after 15 Gy irradiation. In contrast, the effect of 15 Gy on the RIF-1 fibrosarcomas, which give a relatively slow baseline R2* and negligible DeltaR2* response to carbogen prior to treatment, showed a much smaller growth inhibition (143 +/- 3% with air, 133 +/- 12% with carbogen). Quantitation of tumor R2* and carbogen-induced DeltaR2* by MGRE MRI provides completely noninvasive prognostic indicators of a potential acute radiotherapeutic response.