Hyperoxic BOLD-MRI-Based Characterization of Breast Cancer Molecular Subtypes Is Independent of the Supplied Amount of Oxygen: A Preclinical Study

oleh: Silvester J. Bartsch, Viktoria Ehret, Joachim Friske, Vanessa Fröhlich, Daniela Laimer-Gruber, Thomas H. Helbich, Katja Pinker

Format: Article
Diterbitkan: MDPI AG 2023-09-01

Deskripsi

Hyperoxic BOLD-MRI targeting tumor hypoxia may provide imaging biomarkers that represent breast cancer molecular subtypes without the use of injected contrast agents. However, the diagnostic performance of hyperoxic BOLD-MRI using different levels of oxygen remains unclear. We hypothesized that molecular subtype characterization with hyperoxic BOLD-MRI is feasible independently of the amount of oxygen. Twenty-three nude mice that were inoculated into the flank with luminal A (<i>n</i> = 9), Her2<sup>+</sup> (<i>n</i> = 5), and triple-negative (<i>n</i> = 9) human breast cancer cells were imaged using a 9.4 T Bruker BioSpin system. During BOLD-MRI, anesthesia was supplemented with four different levels of oxygen (normoxic: 21%; hyperoxic: 41%, 71%, 100%). The change in the spin–spin relaxation rate in relation to the normoxic state, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msub><mi>R</mi><mn>2</mn></msub><msup><mrow></mrow><mo>*</mo></msup></mrow></semantics></math></inline-formula>, dependent on the amount of erythrocyte-bound oxygen, was calculated using in-house MATLAB code. <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msub><mi>R</mi><mn>2</mn></msub><msup><mrow></mrow><mo>*</mo></msup></mrow></semantics></math></inline-formula> was significantly different between luminal A and Her2<sup>+</sup> as well as between luminal A and triple-negative breast cancer, reflective of the less aggressive luminal A breast cancer’s ability to better deliver oxygen-rich hemoglobin to its tissue. Differences in <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mo>Δ</mo><msub><mi>R</mi><mn>2</mn></msub><msup><mrow></mrow><mo>*</mo></msup></mrow></semantics></math></inline-formula> between subtypes were independent of the amount of oxygen, with robust distinction already achieved with 41% oxygen. In conclusion, hyperoxic BOLD-MRI may be used as a biomarker for luminal A breast cancer identification without the use of exogenous contrast agents.