FDG--a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer.
ABSTRACT Experimental data suggest that the accumulation of [(18)F]fluorodeoxyglucose (FDG) in malignant tumours is related to regional hypoxia. The aim of this study was to evaluate the clinical potential of FDG positron emission tomography (PET) to assess tumour hypoxia in comparison with [(18)F]fluoromisonidazole (FMISO) PET and pO(2)-polarography.
Twenty-four patients with head and neck malignancies underwent FDG PET, FMISO PET, and pO(2)-polarography within 1 week. Parameters of pO(2)-polarography were the relative frequency of pO(2) readings <or=2.5 mmHg, <or=5 mmHg and <or=10 mmHg, respectively, as well as the mean and median pO(2).
We observed a moderate correlation of the maximum standardised uptake value (SUV) of FDG with the tumour to blood ratio of FMISO at 2 h (R=0.53, p<0.05). However, SUV of FDG was similar in hypoxic and normoxic tumours as defined by pO(2)-polarography (6.9+/-3.2 vs 6.2+/-3.0, NS), and the FDG uptake was not correlated with the results of pO(2)-polarography. The retention of FMISO was significantly higher in hypoxic tumours than in normoxic tumours (tumour to muscle ratio at 2 h: 1.8+/-0.4 vs 1.4+/-0.1, p<0.05), and the FMISO tumour to muscle ratio showed a strong correlation with the frequency of pO(2) readings <or=5 mmHg (R=0.80, p<0.001).
These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.
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ABSTRACT: To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), (18)F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (≥1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of ≥1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO ≥1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of ≥1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0-0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT.Journal of Radiation Research 04/2013; · 1.45 Impact Factor
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ABSTRACT: Accurate imaging to identify hypoxic regions in tumors is key for radiotherapy planning. [F-18]‑fluoro-misonidazole ([F-18]-FMISO) is widely used for tumor hypoxia imaging and has the potential to optimize radiotherapy planning. However, the biological characteristics of intratumoral [F-18]-FMISO distribution have not yet been fully investigated. In hypoxic cells, the hypoxia-inducible factor-1 (HIF-1) target proteins that induce cellular proliferation and glucose metabolism, glucose transporter-1 (Glut-1) and hexokinase-II (HK-II), are upregulated. In this study, we determined the intratumoral distribution of [F-18]-FMISO by autoradiography (ARG) and compared it with pimonidazole uptake, expression of Glut-1, tumor proliferative activity (Ki-67 index) and glucose metabolism ([C-14]2-fluoro-2-deoxy-D-glucose uptake; [C-14]-FDG) in a glioma rat model. Five C6 glioma‑bearing rats were injected with [F-18]-FMISO and [C-14]-FDG. After 90 min, the rats were injected with pimonidazole and 60 min later, the rats were sacrificed and tumor tissues were sectioned into slices. The adjacent slices were used for ARG and immunohistochemical (IHC) analyses of pimonidazole, Glut-1 and Ki-67. [F-18]-FMISO ARG images were divided into regions of high [F-18]-FMISO uptake (FMISO+) and low [F-18]-FMISO uptake (FMISO-). Pimonidazole and Glut-1 expression levels, Ki-67 index and [C-14]-FDG distribution were evaluated in the regions of interest (ROIs) placed on FMISO+ and FMISO-. [F-18]-FMISO distribution was generally consistent with pimonidazole distribution. The percentage of positively stained areas (% positive) of Glut-1 in FMISO+ was significantly higher compared to FMISO- (24±8% in FMISO+ and 9±4% in FMISO-; P<0.05). There were no significant differences in Ki-67 index and [C-14]-FDG uptake between FMISO+ and FMISO- (for Ki-67, 10±5% in FMISO+ and 12±5% in FMISO-, P = ns; for [C-14]-FDG, 1.4±0.3% ID̸g̸kg in FMISO+ and 1.3±0.3% ID̸g̸kg in FMISO-, P = ns). Intratumoral [F-18]-FMISO distribution reflected tumor hypoxia and expression of the hypoxia‑related gene product Glut-1; it did not, however, reflect tumor proliferation or glucose metabolism. Our findings help elucidate the biological characteristics of intratumoral [F-18]-FMISO distribution that are relevant to radiotherapy planning.International Journal of Oncology 01/2013; · 2.66 Impact Factor
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ABSTRACT: Cancers of the head and neck are a malignancy causing a considerable health burden. In head and neck cancer patients, tumor hypoxia has been shown to be an important predictor of response to therapy and outcome. Several imaging modalities can be used to determine the amount and localization of tumor hypoxia. Especially PET has been used in a number of studies analyzing this phenomenon. However, only few studies have reported the characteristics and development during (chemoradio-) therapy. Yet, the characterization of tumor hypoxia in the course of treatment is of great clinical importance. Successful delineation of hypoxic subvolumes could make an inclusion into radiation treatment planning feasible, where dose painting is hypothesized to improve the tumor control probability. So far, hypoxic subvolumes have been shown to undergo changes during therapy; in most cases, a reduction in tumor hypoxia can be seen, but there are also differing observations. In addition, the hypoxic subvolumes have mostly been described as geographically rather stable. However, studies specifically addressing these issues are needed to provide more data regarding these initial findings and the hypotheses connected with them.Frontiers in Oncology 01/2013; 3:223.