Background: SR4554 is a fluorine-containing 2-nitroimidazole, designed as a hypoxia marker detectable with 19 F magnetic resonance spectroscopy (MRS). In an initial phase I study of SR4554, nausea/vomiting was found to be dose-limiting, and 1400 mg m −2 was established as MTD. Preliminary MRS studies demonstrated some evidence of 19 F retention in tumour. In this study we investigated higher doses of SR4554 and intratumoral localisation of the 19 F MRS signal. Methods: Patients had tumours ⩾3 cm in diameter and ⩽4 cm deep. Measurements were performed using 1 H/ 19 F surface coils and localised 19 F MRS acquisition. SR4554 was administered at 1400 mg m −2 , with subsequent increase to 2600 mg m −2 using prophylactic metoclopramide. Spectra were obtained immediately post infusion (MRS no. 1), at 16 h (MRS no. 2) and 20 h (MRS no. 3), based on the SR4554 half-life of 3.5 h determined from a previous study. 19 Fluorine retention index (%) was defined as (MRS no. 2/MRS no. 1)*100. Results: A total of 26 patients enrolled at: 1400 ( n =16), 1800 ( n =1), 2200 ( n =1) and 2600 mg m −2 ( n =8). SR4554 was well tolerated and toxicities were all ⩽grade 1; mean plasma elimination half-life was 3.7±0.9 h. SR4554 signal was seen on both unlocalised and localised MRS no. 1 in all patients. Localised 19 F signals were detected at MRS no. 2 in 5 out of 9 patients and 4 out of 5 patients at MRS no. 3. The mean retention index in tumour was 13.6 (range 0.6–43.7) compared with 4.1 (range 0.6–7.3) for plasma samples taken at the same times ( P =0.001) suggesting 19 F retention in tumour and, therefore, the presence of hypoxia. Conclusion: We have demonstrated the feasibility of using 19 F MRS with SR4554 as a potential method of detecting hypoxia. Certain patients showed evidence of 19 F retention in tumour, supporting further development of this technique for detection of tumour hypoxia.

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