Clinical Research On Hypoxia Imaging With 18F-FETNIM PET/CT For Non-small Cell Lung Cancer

Part one Preliminary Clinical Study of Hypoxia Imaging with ¹⁸F-FETNIMPET/CT on NSCLCObjective: Fluorine-18 fluoroerythronitroimidazole (¹8)F-FETNIM) is anitroimidazole compound that is potentially useful as a hypoxia marker in positronemission tomography (PET) studies of oncological patients. The aim of our study was to evaluate the security of clinical use of FETNIM, the feasibility of hypoxia imagingin detecting human tumor hypoxia and the influence of imaging time point on images.Materials and Methods: From April 2005 to October 2006, 26 patients withpathologically proven NSCLC were prospectively included in the study. All patientsgave written informed consent before entering the study. FETNIM PET/CT scan (GEDiscovery LS PET/CT) was performed in all 26 patients 3 days before radiotherapy.Images were collected 30mins, 60mins and 120rains after intravenous (â…³) injectionapproximately 7.4MBq/Kg FETNIM. For FETNIM PET/CT, tumor-to-muscle ratiosof the regional radioactivity concentrations were calculated, using the transverseplane with the maximum FETNIM uptake and manually drawn regions of interest ofthe tumor and the ipsilateral muscles. The data were analyzed with SPSS 11.0software.Results: After injection of FETNIM, no adverse or subjective side effects werenoticed in any of the subjects. The images in 4 cases were negative, the other 22 werepositive that FETNIM PET/CT images showed local uptake in thoracic lesions. Theimages were clearly identified and images at 1 hour were the clearest. There were 15cases of squamous carcinoma and 7 cases of adenocarcinoma in 22 patients withpositive FETNIM imagings. The average T/M value and SUVmax at lh of squamouscell carcinoma cases and adenocarcinoma cases were 1.634±0.35, 2.424±0.41 and1.994±1.48, 2.774±0.79 respectively (P=0.41, P=0.20). Conclusions: FETNIM is a good hypoxia-imaging agent which clinical use is safeand satisfactory. The preliminary study provides valuable methods and experience toits further research.Part two ¹⁸F-FETNIM Hypoxia Imaging and ¹⁸F-FDG Metabolic Imaging onNSCLC: A Comparative StudyObjective: Tumor tissue oxygenation was measured with ¹⁸F-FETNIM PET/CT,whereas tumor glucose metabolism was measured with ¹⁸F-FDG PET/CT. The aim ofthe study was to compare the hypoxia imaging and metabolic imaging using FETNIMand FDG PET/CT respectively. It has evidence that acute hypoxia increase glycolysisand chronic hypoxia decrease the cell metabolism. Our study was to validate thecorrelation of the uptakes of FETNIM and FDG.Materials and Methods: From April 2005 to October 2006, 11 NSCLC patientspreviously obtained positive FETNIM images were prospectively included in thestudy. FDG PET/CT imaging scans were performed in all patients 3 days beforeradiotherapy respectively. Maximum standardized uptake values of the FDG uptakeof the tumor were calculated after normalization of the radioactivity concentration to the injected radioactivity and the body weight. The relations of FDG and FETNIMPET/CT imaging were analyzed with SPSS 11.0 software.Results: The coefficients was 0.16 between the SUV_max of FETNIM and FDG. Thecorrelation of SUV_max in FDG and T/M in FETNIM was very small (Spearman r=0.24). There were 4 types of relations between uptakes in FDG and FETNIM. (1) lowdegree of hypoxia and low glucose metabolism, (2) low degree of hypoxia but highglucose metabolism, (3) high degree of hypoxia and high glucose metabolism, (4)high degree ofhypoxia but low glucose metabolism.Conclusions: Hypoxia is a general factor affecting glucose metabolism; however,some hypoxic tumors can have modest glucose metabolism, whereas some highlymetabolic tumors are not hypoxic.Part Three Clinical Research on ¹⁸F-FETNIM and ¹⁸F-FDG PET/CT Imaging inRadiotherapy Response Evaluation of NSCLCObjective: Hypoxia is a characteristic feature in malignant tumors. Tumor hypoxiacan influence response to radiotherapy and other treatment modalities, oxygenation status proving to be a prognostic indicator of the outcome of radiotherapy. ¹⁸F-FDGPET/CT is being widely used in clinical oncology, it has become evident that the rateof glycolysis, as captured by the SUV_max or related uptake measures, is an importantpredictor of the biological aggressiveness in multiple tumor types. The aim of thestudy was to evaluate the feasibility of FETNIM and FDG PET/CT imaging inpatients with NSCLC in relation to radiotherapy response.Materials and Methods: From April 2005 to October 2006, 26 patients withpathologically proven NSCLC were prospectively included in the study. All patientswere performed FETNIM imaging scans in 3 days before radiotherapy. Additionally,11 patients were also performed FDG PET/CT scans. Tumor response was evaluatedby FDG PET/CT (using visual assessment of response by tumor volume), accordingto standard WHO criteria. SUV of FDG and FETNIM in relations to radiotherapyresponse were analyzed with SPSS 11.0 software.Results: 26 patients were performed FETNIM PET/CT imaging, 22 of which werepositive. The median T/M value and SUV_max of 22 patients were 1.57 and 2.57respectively. The effective rate of the cases with low degree of hypoxia was higherthan those with high degree of hypoxia (P=0.024, P=0.183). The median SUV_max inFDG PET/CT images of 22 patients was 12.32. The effective rate in patients with lowSUV_max was higher than those with high SUV_max (P=0.183).Conclusions: Tumor glucose metabolism and hypoxia degree are essential predictors to radiotherapy response, but the role of prediction to long-term survival still needsfurther study.