Regional tumor oximetry: ₁₉F NMR spectroscopy of hexafluorobenzene

Purpose: An accurate method for monitoring oxygen tension (pO₂) of individual tumors could be valuable for optimizing treatment plans. We have recently shown that ₁₉F nuclear magnetic resonance (NMR) spin-lattice relaxometry of hexafluorobenzene (HFB) provides a highly sensitive indicator of tumor oxygenation. We have now refined the methodology to provide enhanced precision, and applied the method to investigate dynamic changes in tumor oxygenation. Methods and Materials: Dunning prostate adenocarcinoma R3327- AT1 was grown in the form of pedicles on the foreback of male Copenhagen rats. When the tumors reached ≃1 cm diameter, HFB (20 μl) was administered, either centrally or peripherally, by direct intratumoral (IT) injection. Local pO₂ was determined using pulseburst saturation recovery (PBSR) ₁₉F NMR spectroscopy on the basis of the spin-lattice relaxation rate, R1. Results: Interrogation of the central region of tumors provided typical values in the range pO₂ = 1.4-6.4 mmHg, with a typical stability of ±2 mmHg over a period of 20 min, when rats breathed 33% O₂. Altering the inhaled gas to oxygen or carbogen (95% 0₂/5% CO₂) produced no significant change. In contrast, interrogation of tumor periphery indicated baseline pO₂ in the range 7.9-78.9 mmHg. Altering inspired gas produced significant changes (p < 0.0001) with O₂ or carbogen, although the change was generally greater with carbogen. In each case, pO₂ returned to baseline within 16 min of returning the inhaled gas to baseline. Conclusion: We believe this method provides a valuable new approach with the requisite precision and accuracy to investigate tumor pO₂.