Abstract
Accelerated repopulation has been observed in various tumors. This study was aimed to evaluate the potential of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) uptake and Computed Tomography Number (CTN) in monitoring tumor responses to radiotherapy compared with tumor volume (TV) changes. Tumor bearing nude mice were assigned to either irradiated daily or every second day group and then randomized to 6 sub-groups to receive 0Gy, 6Gy, 12Gy, 18Gy, 24Gy, 36Gy irradiation, respectively. TV was measured every 3 days. 18F-FLT micro-PET/CT scans were performed after irradiation being completed. Tumor sections were stained to calculate the immunohistochemical (Ki-67) labeling index (LI). Comparison analysis between FLT uptake parameters, CTNs, VTs and Ki-67 LI results were conducted to determine the correlation. Ki-67 LI increased significantly after 6 times of irradiation at irradiated daily group and after 3 times at irradiated every second day group, suggesting accelerated repopulation. No shrinkage of TV was noticed at two groups during irradiation delivery. Both 18F-FLT uptake and CTN increased significantly after irradiation of 12Gy/6f/6d and 6Gy/3f/6d. Comparison analysis found a significant relationship between Ki-67 LI and 18F-FLT uptake parameters as well as CTN. Both 18F-FLT PET and CT have the potential to reflect the tumor proliferative response during radiation delivery.
Highlights
Anticancer treatment has translated from simple nonspecific cytotoxic therapy to ever-more-sophisticated specific individualized therapeutics
Feng et al have ever investigated CT number (CTN) changes of gross tumor volume (GTV) according to daily diagnostic-quality CT-on-rails acquired during CT-guided intensity modulated radiation therapy in head and neck cancer patients, and found a fair correlation between Computed Tomography Number (CTN) reduction and radiation doses[15]
In this work we conducted a study to investigate the TVs, 18F-FLT uptake parameters, CTN changes of tumors according to repetitive position-emission tomography (PET)/CT scans and pathological evaluations for human A549 lung adenocarcinoma tumor-bearing BALB/c nude mice
Summary
Anticancer treatment has translated from simple nonspecific cytotoxic therapy to ever-more-sophisticated specific individualized therapeutics. Appearance of various image-guided technologies allows for more noninvasive, precise, quantitative, in vivo methods to detect the inter-fraction variations of tumors during RT delivery, ranging from anatomic, histologic changes to metabolic, molecular, functional changes. Among those emerging methods, 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) position-emission tomography (PET) with the capacity to www.nature.com/scientificreports/. Feng et al have ever investigated CT number (CTN) changes of gross tumor volume (GTV) according to daily diagnostic-quality CT-on-rails acquired during CT-guided intensity modulated radiation therapy in head and neck cancer patients, and found a fair correlation between CTN reduction and radiation doses[15] This implied the potential of CTN as an early surrogate biomarker to evaluate tumor response. An effort will be made to examine the relationships between TV regressions, 18F-FLT parameters, CTN changes, and delivered radiation doses and to determine whether these changes could potentially help predict the re-proliferation of tumor
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