Examining correlations of oxygen sensitive MRI (BOLD/TOLD) with [¹⁸F]FMISO PET in rat prostate tumors

Hypoxia is regarded as a potential prognostic biomarker for tumor aggressiveness, progression, and response to therapy. The radiotracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) has been used with positron emission tomography (PET) to reveal tumor hypoxia. Meanwhile, blood oxygen level dependent (BOLD) MRI and tissue oxygen level dependent (TOLD) MRI offer insight into oxygenation based on endogenous signals without the need for radiolabels. Here, we compared BOLD and TOLD MRI with [¹⁸F]FMISO uptake using Dunning prostate R3327-AT1 tumor bearing rats. BOLD and TOLD MRI were acquired with respect to an oxygen gas breathing challenge. The following day, dynamic PET was performed up to 90 minutes following IV injection of [¹⁸F]FMISO. Tumors showed distinct heterogeneity based on each technique. Correlations were observed between magnitude of mean BOLD or TOLD MRI signal responses to oxygen-breathing challenge and initial distribution of [¹⁸F]FMISO. Correlations were observed for whole tumor as well on a regional basis with stronger correlations in the well perfused tumor periphery indicating the strong influence of perfused vasculature. After 90 minutes most correlations with signal intensity became quite weak, but correlations were observed between hypoxic fraction based on FMISO and fractions of tumor showing BOLD or TOLD response in a subset of tumors. This emphasizes the importance of considering regional heterogeneity and responsive fractions, as opposed to simple magnitudes of responses. Although the data represent a small cohort of tumors they present direct correlations between oxygen sensitive MRI and PET hypoxia reporter agents in the same tumors, indicating the potential utility of further investigations.