Exploring Δr2* and Δr1 as imaging biomarkers of tumor oxygenation

Abstract

Purpose To investigate the combined use of hyperoxia-induced ΔR 2* and ΔR1 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 R2* and R1 before and during carbogen (95% O2/5% CO 2) challenge, and correlates of ΔR2* and ΔR1 assessed. Results Mean baseline R2* and R1 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 ΔR2* and ΔR1 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 ΔR 2* and ΔR1 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 ΔR2*. PC3 tumors were less hypoxic at baseline, and their response to carbogen dominated by increased dissolved oxygen, evidenced by highly positive ΔR 1. Because the two biomarkers are sensitive to different oxygenation ranges, the combination of ΔR2* and ΔR1 may better characterize tumor hypoxia than each alone. © 2013 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.