Assessment Of Response Of Intracranial Tumor To Radiotherapy By PET Imaging Of Apoptosis

Objective:The purpose of this study was to investigate the performance of 18F-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (18F-ML-10), a novel PET radiotracer for apoptosis, as a tool for observe the early apoptosis and distribution for Cyberknife treatment of intracranial tumors.Datas of early changes in 18F-ML-10 uptake and subsequent changes (2-4 months after treatment) in tumor anatomical dimensions were collected, and their correlation was analyzed.The feasibility of 18F-ML-10 as a tool for the early detection of response of intracranial tumors to Cyberknife treatment was discussed preliminary.Methods:From January 2014 to December 2015,29 patients (30 lesions) diagnosed (imaging diagnosis or pathologic diagnosis) with intracranial tumors in the people's liberation army general hospital,scheduled to undergo Cyberknife stereotactic radiotherapy,were prospectively enrolled in the study.Strictly according to the integration and elimination standard the subjects were determined with informed consent. All patients underwent PET-CT of apoptosis with 18F-ML-10 before and after(in 48 hours) Cyberknife treatment.For each subject, datas of CT scan and MRI contrast enhancement were acquired before treatment.The acquired CT scan was aligned with theMRI using MIM software (version number:6.5.4), and then were imported into CyberKnife Robotic Radiosurgery System (Multiplan 4.0.2) for delineating the target, organs at risk. Then, the MRI scan with data of target was coregistered to the baseline PET scan and follow-up PET scan. The parametric maps of the target were optionally projected on the PET scans as a region of interest (ROI), and the values ofradioactivity(bq/ml)for each voxel in the ROI were collected separately on baseline PET scan and follow-up PET scan. The percentage change in each voxels was then calculated.Voxel-based subtractionPETimages were acquired using MIM software forvisualanalysistoobserve the changes of cell apoptosis before and afterthetreatment. Changes in tumor anatomical dimensions on MRI were acquired, and correlation between early changes in 18F-ML-10 uptake and subsequent changes in tumor anatomical dimensions were analyzed. Complaints and complications were concerned during therapy and follow-up period.Results:Twenty-nine patients (30 lesions) treated with CK at 14-24Gy in 1-3 fractions completed the trial finally. By PET imaging of apoptosis with 18F-ML-10,tumors showed clear boundary, and locational exactly. Changes of cell apoptosis in tumors before and after the treatment and heterogeneity in tumors were observed clearly on voxel-based subtraction PET images. A highly significant correlation was observed between the change in 18F-ML-10 uptake in the tumor measured early during treatment(X) and the subsequent change in tumor mass measured at 2-4months after completion of CK treatment(Y). The Pearson correlation coefficient was found to be very high (r=0.862, p<0.05).And the regression equation was Y=1.018*X-0.016.No drug complications, radiation damages or injury of brain function was appeared during therapy and follow-up period.Conclusions:Tumors can be showed clearly on PET imaging of apoptosis with 18F-ML-10,and locational exactly.Uptake in normal brain tissue is far lower than that in tumors.Tumor tissues and surrounding edema can be identified easily.18F-ML-10 PET scans may provide a novel approach for early response assessment in intracranial tumors. Significant correlation was found between the change in 18F-ML-10 uptake in the tumor measured early during treatment and the subsequent change in tumor mass measured after completion of CK treatment.CK for the treatment of intracranial tumors has the advantages of high safety, evident efficacy.