Correlating quantitative MR measurements of standardized tumor lines with histological parameters and tumor control dose.
OBJECTIVE
To correlate non-invasively acquired radiobiologically relevant magnetic resonance (MR) parameters with functional histology and tumor control doses (TCD(50)).


METHODS
The MR parameters relative perfusion, re-oxygenation and lactate (Lac) concentration from eight human xenograft squamous tumor lines were compared with the histologically acquired pimonidazole hypoxic fraction, the perfused vessel area and TCD(50).


RESULTS
Good spatial correlation in the parameter maps could be observed between the pimonidazole staining and tumor regions, which can be reoxygenated when breathing carbogen. A strong positive correlation (R=0.74) was found between whole tumor pimonidazole hypoxic fraction and re-oxygenation, as one would expect. A good correlation was also observed between Lac concentration and re-oxygenation (R=0.71) and between TCD(50) and re-oxygenation (R=0.64), whereas Lac and TCD(50) showed a moderate relation (R=0.44). The in vivo measurement of relative perfusion could be validated to reflect the perfused vessel area (R=0.63). No correlation was detected between perfusion and re-oxygenation or TCD(50).


CONCLUSIONS
Lac and re-oxygenation were shown to be pretreatment predictive markers independent from the pathophysiological changes induced during a fractionated course of radiotherapy. These parameters hold promise to be acquired non-invasively with results just a few minutes after measurement and to tailor radiotherapy to individual patterns of a tumor microenvironment.
Mörchel
Philipp
P
Department of Physics, University of Würzburg, Würzburg, Germany. moerchel@physik.uni-wuerzburg.de
Melkus
Gerd
G
Yaromina
Ala
A
Zips
Daniel
D
Baumann
Michael
M
Jakob
Peter M
PM
Flentje
Michael
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000528:radiation effects; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism* / Q000528:radiation effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009593:Nitroimidazoles / Q000494:pharmacology; D010101:Oxygen Consumption / Q000528:radiation effects; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D019344:Lactic Acid; C033815:pimonidazole