title: Exploring ΔR(2) * and ΔR(1) as imaging biomarkers of tumor oxygenation.
abstract: OBJECTIVE
  To investigate the combined use of hyperoxia-inducedΔR(2) * and ΔR(1) as a noninvasive imaging biomarker of tumor hypoxia.
  
  
  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% O2 /5% CO2 ) challenge, and correlates of ΔR(2) * and ΔR(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 ΔR(2) * and ΔR(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 betweenΔR(2) * and ΔR(1) was revealed.
  
  
  CONCLUSIONS
  Considering the blood oxygen-hemoglobin dissociation curve, fast R2 * suggested that GH3 prolactinomas were more hypoxic at baseline, and their carbogen response dominated by increased hemoglobin oxygenation, evidenced by highly negative ΔR(2) *. 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 ΔR(2) * and ΔR(1) may better characterize tumor hypoxia than each alone.
authors.affiliation: Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom.
authors.forename: Jake S
authors.initials: JS
authors.lastname: Burrell
authors.forename: Simon
authors.initials: S
authors.lastname: Walker-Samuel
authors.forename: Lauren C J
authors.initials: LC
authors.lastname: Baker
authors.forename: Jessica K R
authors.initials: JK
authors.lastname: Boult
authors.forename: Yann
authors.initials: Y
authors.lastname: Jamin
authors.forename: Jane
authors.initials: J
authors.lastname: Halliday
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
mesh_terms: D000465:Algorithms; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism*; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D010100:Oxygen
keywords: MRI; biomarker; hypoxia; tumor; ΔR1; ΔR2*