Exploring R2* and R1 as imaging biomarkers of tumor oxygenation

Purpose: To investigate the combined use of hyperoxia-induced R-2* and R-1 as a noninvasive imaging biomarker of tumor hypoxia. Materials and Methods: MRI was performed on rat GH3 prolactinomas (n = 6) and human PC3 prostate xenografts (n = 6) propagated in nude mice. multiple gradient echo and inversion recovery truefisp images were acquired from identical transverse slices to quantify tumor R-2* and R-1 before and during carbogen (95% O-2/5% CO2) challenge, and correlates of R-2* and R-1 assessed. Results: Mean baseline R-2* and R-1 were 119 +/- 7 s(-1) and 0.6 +/- 0.03 s(-1) for GH3 prolactinomas and 77 +/- 12 s(-1) and 0.7 +/- 0.02 s(-1) for PC3 xenografts, respectively. During carbogen breathing, mean R-2* and R-1 were -20 +/- 8 s(-1) and 0.08 +/- 0.03 s(-1) for GH3 and -0.5 +/- 1 s(-1) and 0.2 +/- 0.08 s(-1) for the PC3 tumors, respectively. A pronounced relationship between R-2* and R-1 was revealed. Conclusion: Considering the blood oxygen-hemoglobin dissociation curve, fast R-2* suggested that GH3 prolactinomas were more hypoxic at baseline, and their carbogen response dominated by increased hemoglobin oxygenation, evidenced by highly negative R-2*. PC3 tumors were less hypoxic at baseline, and their response to carbogen dominated by increased dissolved oxygen, evidenced by highly positive R-1. Because the two biomarkers are sensitive to different oxygenation ranges, the combination of R-2* and R-1 may better characterize tumor hypoxia than each alone. J. Magn. Reson. Imaging 2013;38:429-434. (c) 2013 Wiley Periodicals, Inc.