Exploring R-2* and R-1 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% CO(2) ) 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;. � 2013 Wiley Periodicals, Inc.