A prospective clinical trial of tumor hypoxia imaging with 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) before and during radiation therapy

摘要

Between November 2009 and April 2011, 10 patients scheduled for RT for primary or recurrent tumors were enrolled in this prospective study. Eligible patients had histologically proven malignant tumors, with a performance status (PS) level of 0–1 and were aged 20–80 years. Patients without gross target volume, pregnant or lactating women, and patients with mental disorders or severe organ disorders were excluded. Patient and tumor characteristics are summarized in Table 1. Ten patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with non-small-cell lung cancer, and one with uterine body cancer, were included. The initial tumor response for both primary tumors and metastatic lymph nodes was evaluated by CT, magnetic resonance imaging (MRI), and clinical examination 1–2 months after the end of treatment according to the RECIST criteria (version 1.1) [11]. Because some tumors regress slowly, tumor response was evaluated at the maximum tumor regression between 1 and 2 months of treatment. Each patient was scanned with an integrated PET/CT unit (Biograph/Somatom Emotion Duo, Siemens Medical Solutions, Hoffmann Estates, IL, USA). All PET images were acquired using a matrix of 128 × 128 pixels. The time for one bed position (162 mm in z-direction) scan was 120–150 sec. At a distance of 10 cm from the center of the field of view (FOV), the full-width at half maximum (FWHM) reached 7.4 mm × 7.4 mm × 7.1 mm, in the x, y and z directions, respectively. Voxel dimensions were 4.5 mm × 4.5 mm × 2.0 mm. CT scans were acquired in the spiral mode, with a slice thickness of 2–5 mm, a pitch of 6 mm, 130 kv and 55 mAs. The translation speed of the couch was 7.4 mm/sec. As a protocol, F-MISO PET/CT was performed twice before RT and during fractionated RT of ～ 20 Gy/10 fractions. Patients were injected intravenously with 7.4 MBq/kg of F-MISO. No fasting period before F-MISO injection was required. PET/CT was obtained twice, at 100 and 180 min after injection of F-MISO. For all patients, F-MISO PET/CT was performed before the start of RT, but this information was not used for the treatment planning. Eight patients were treated as definitive RT with a planned total dose of 60–70 Gy/30–35 fractions, although one patient terminated RT at 42 Gy due to acute renal failure caused by chemotherapy. The remaining two patients with gastrointestinal cancer were treated with preoperative chemo-RT (CRT) in 45–50 Gy/25 fractions, and curative resection could be done following CRT for these patients. All patients except for a patient with recurrence of uterine body cancer were treated with concurrent chemotherapy. Details of the chemotherapy are summarized in Table 1. During RT, 2–3 cycles of chemotherapy were given. Because normal tissues are considered to be under normoxia, F-MISO SUVs of normal muscles were measured. Data were processed with a Siemens e.soft workstation to measure SUV and hypoxic volume. In placing the volumetric regions of interest (VOIs) over the tumor and normal muscle, the SUVmax of the VOI on PET images was adjusted by referring to CT images and PET/CT fusion images. SUVmax in 108 normal muscle areas was measured for all 18 F-MISO studies. For each study, six oval VOIs of 10–20 cm3 were measured on bilateral posterior neck muscles (multifidus muscles, semispinalis capitis muscle, and semispinalis cervicis muscle), bilateral back muscles (erector spinae muscle, rhomboid major muscle, and trapezius muscle), or bilateral buttock muscles (gluteus maximus muscle).