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


METHODS
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.


RESULTS
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).


CONCLUSIONS
Quantitation of tumor R2* and carbogen-induced DeltaR2* by MGRE MRI provides completely noninvasive prognostic indicators of a potential acute radiotherapeutic response.
Rodrigues
Loreta M
LM
Cancer Research UK Biomedical Magnetic Resonance Research Group, Department of Basic Medical Sciences, St. George's Hospital Medical School, London, United Kingdom.
Howe
Franklyn A
FA
Griffiths
John R
JR
Robinson
Simon P
SP
D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism; D011379:Prognosis; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D051381:Rats; D011920:Rats, Inbred WF
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen