Tumor Hypoxia Imaging With [F‐18] Fluoronitroimidazole in Non‐small‐cell Lung Cancer

To the Editor: Because the response to anticancer drugs is different in elderly patients with lung cancer than it is in younger patients, a reliable and simple method1 to predict the response to chemotherapy is needed. Arterial blood carboxyhemoglobin concentration is a useful biomarker for response to chemotherapy and survival in elderly patients with non-small-cell lung cancer (NSCLC).2,3 Furthermore, hypoxic conditions in solid cancer are associated with resistance to cancer therapy.4 Dr. JG Rajendran and colleagues recently reported that tumor hypoxia was identified in head and neck cancer using [F-18]-fluoromisonidazole (FMISO) positron emission tomography (PET) and that pretherapy FMISO uptake was strongly associated with poor prognosis in those patients (Figure 1).5 Nitroglycerin treatment before chemotherapy reduced hypoxia-induced chemoresistance via an increase in tumor oxygenation in NSCLC,6,7 so the close relationship between an increase in pretherapy FMISO uptake in tumor tissues and poor prognosis5 seems to be natural. Therefore, a novel hypoxic imaging method using [F-18]-FRP170:1-(2-fluoro-1-[hydroxymethyl]-ethoxy)-methyl-2-nitroimidazole for solid cancers including NSCLC has been developed at Tohoku University School of Medicine8,9 to noninvasively study a relationship between distribution of hypoxic area and tumor characteristics in vivo. The upper layer shows chest computed tomography (CT) scan in a patient with lung adenocarcinoma (60-year-old man, cT2N3M0, Stage IIIB, maximum tumor diameter 65 mm). The middle layer shows a [F-18]-FRP170, 1-(2-fluoro-1-[hydroxymethyl]-ethoxy)-methyl-2-nitroimidazole positron emission tomography (PET) scan. The maximum standardized uptake value of [F-18]-FRP170-PET was high (2.0). The lower layer shows the merged pictures, which are composed of a chest CT scan and an [F-18]-FRP170-PET scan. The distribution of tumor hypoxia was estimated using [F-18]-FRP170 PET in nine patients (mean age±standard error 72.8±3.3, female/male=3/6) with NSCLC between September 1, 2005, and June 6, 2006, at the Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. This compound was synthesized by [F-18]-labeling of RP170, which was developed as a new hydrophilic 2-nitroimidazole analog.8 Seven of nine patients had lung adenocarcinoma (2 in Stage IA, 1 in IIA, 3 in IIIB, and 1 in IV). Two of nine patients had squamous cell carcinoma (IIIB and IV). Dynamic whole-body emission scans for patients were performed approximately 120 minutes after an intravenous bolus injection of 185 Mbq of [F-18]-FRP170 using a Biograph DUO scanner (Siemens, Knoxville, TN). Maximum standardized uptake values (SUVs) were obtained by drawing regions of interest on the PET images for tumor tissues divided by those for thoracic muscles. Furthermore, primary tumor volume was measured according to chest computed tomography scan, and maximum SUV of [F-18]-fluoro-2-deoxy-d-glucose (FDG)-PET in the tumor tissues was measured. The Ethics Committee of Tohoku University School of Medicine approved this study, and written informed consent was obtained from each subject. The maximum SUV of [F-18]-FRP170-PET for tumor tissues was significantly higher than that for normal lung tissues (1.37±0.22 vs 0.38±0.02, P=.002) and significantly correlated with tumor volumes (53,438±18,772 mm3) (r=0.90, P<.001). Furthermore, the maximum SUV of [F-18]-FRP170-PET for tumor tissues was significantly correlated with that of FDG-PET (7.12±1.32, r=0.75, P=.02). In the current study, tumor hypoxia estimated using [F-18]-FRP170-PET was consistent with that using FMISO-PET.5 Maximum SUV of [F-18]-FRP170-PET also correlated with that of FDG-PET. The precise reason is unclear, but the maximum SUV of FDG-PET was reported to inversely associate with response and times to relapse after neoadjuvant chemotherapy in NSCLC.10 A high maximum SUV of [F-18]-FRP170-PET for tumor tissues, as well as that of FDG-PET, may be an indicator of resistance to cancer therapy. We thank Mr. Grant Crittenden for the English correction. Financial Disclosure: Dr. Yasuda was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture (17790524) of the Japanese government. Dr. Yamaya was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture (16590732) and the Ministry of Welfare and Labor of the Japanese government. Author Contributions: Dr. Yasuda and Dr. Nakayama: study concept and design, acquisition of data, analysis and interpretation of data, and preparation of manuscript. Dr. Kaneta and Dr. Takai: study concept and design, acquisition of data, analysis and interpretation of data. Dr. Iwata, Dr. Ito, Dr. Tsujitani, Dr. Takahashi, and Dr. Yanagihara: analysis and interpretation of data. Dr. Yamada: study concept and design. Dr. T. Sasaki: acquisition of data. Dr. Yamaya: study concept and design, analysis and interpretation of data. Sponsor's Role: None.