The Clinical Research Of A New Hypoxia Tracer--¹⁸F-HX4

Purpose:Evaluation the radiolabelation method and clinical safety of 18F-HX4. Materials and Methods:Use the new nitroimidazole compound, HX4, as precursor,18F-radiolabelled via nucleophilic substitution, The final product,18F-HX4, was comfirmed by comparison with standard 19F-HX4 under HPLC. Times of radiolabelation, radiolabeling efficiency and productivity of each time were recorded.16 cases of tumor patient from June 2009 to January 2010 were enrolled in. All the patients underwent the 18F-HX4 PET/CT scan and informed consents were signed in advance. Images were acquired 90min and 120min after injection of 18F-HX4 respectively. Observe the clinical safety 18F-HX4 and image quality of 18F-HX4 PET/CT. Results:18F-HX4 was radiolabeled 15 times totally. The retention time of radioactive peak of 18F-HX4 was consistent with the UV peak of standard 19F-HX4.Radiochemical purity> 98% and specific activity>500GBq/mol.Quality control results were all within the normal range.No adverse reaction was observed after injection among all the 16 patients.The images acquired were clear which show that 18F-HX4 accumulated in tumor tissue selectively.Conclusion:The radiolabelation method of 18F-HX4 was reliable,convenient. The application of 18F-HX4 is clinical safe. Purpose:Compare 18F-HX4 with traditional PET hypoxia imaging agent, 18F-FMISO and compare both of the imaging agent with the endogenous hypoxia markers,CA IX to evaluate the clinical application of 18F-HX4. Materials and Methods:The 16 patients undergoing 18F-HX4 PET/CT in Part I underwent 18F-FMISO PET/CT the second day. Ten Of the 16 patients had surgery later and the tumor resctions were sent to pathology laboratory for immunohistochemical analysis of CA IX expression. Compare the SUVmax and T/M of 18F-HX4 and 18F-FMISO.Correlation analyses between the imaging agents and CA IX were done respectively. Results:In both 18F-HX4 and 18F-FMISO PET/CT, lesions of seven patients show negative and lesions of the other nine patients show positive. While in 18F-HX4 PET/CT the average SUVmax and T/M at 90min and 120min of the 11 positive leisions were 1.31±0.33,1.56±0.42 (90min) and 1.29±0.37,1.67±0.32(120min),the average SUVmax and T/M at 120min in 18F-FMISO were 1.73±0.41,2.00±0.65. The immunohistochemical analysis of CA IX expression showed the positive rate was 81.8% for 11 leisions from 10 patients and the numbers of(-),(+),(++),(+++)were 2,3,3,3 separatedly. There was no significant difference between the images acquired at 90 min and at 120min after injection of 18F-HX4 (t=0.762, p=0.466;t=-1.771,p=0.110).The average SUVmax and T/M of 18F-FMISO were higher than those of 18F-HX4.The SUVmax of 18F-HX4 was highly correlated with CA IX expression and that of 18F-FMISO was moderately correlated with CA IX expression.The T/M of both the imaging agents were not correlated with CA IX expression. Conclusion:Although the SUVmax and T/M of 18F-FMISO were higher than those of 18F-HX4,the correlation between 18F-HX4 and CA IX was higher than that between 18F-FMIO and CA IX. 18F-HX4 can be used as a hypoxia imaging agent which may be better than 18F-FMISO. Purpose:Compare 18F-FDG with 18F-HX4 and CA IX. Analyze the relationship among 18F-FDG,18F-HX4 and CA IX expression. Materials and Methods:12 of the 16 patients undergoing 18F-HX4 PET/CT in Part I underwent 18F-FDG PET/CT the third day. Seven of the 12 patients had surgery. Analyze the correlation of SUVmax of 18F-FDG with SUVmax and T/M of 18F-HX4 for all the 12 patients.For those that had surgery, also analyze the correlation between SUVmax of 18F-FDG and CA IX expression. Results:16 leisions from 12 patients all show 18F-FDG uptake and the average SUVmax was 11.74±5.71.Significant correlation was found neither between 18F-FDG and 18F-HX4,nor between 18F-FDG and CA IX expression.Conclusion:18F-FDG cannot reflect the situation of tumour hypoxia. Combined use of 18F-HX4 and 18F-FDG provide more complete tumor information leading more appropriate therapeutic plan and promising prognosis.