Basic Study Of ¹⁸F-FLT PET/CT In Radiotherapy Of Nasopharyngeal Carcinoma

Objective:1,A rabbit VX2 nasopharyngeal transplanted tumor model has been established to simulate the development of nasopharyngeal tumor in body which can be a appropriate experimental animal model for the study of ¹⁸F-FLT PET/CT in the radiotherapy of nasopharyngeal cancer;2,Scanning the rabbit VX2 nasopharyngeal transplanted tumor model by ¹⁸F-FLT PET/CT and¹⁸F-FDG PET/CT,Measuring the radioactive uptake of tumor region and comparing the uptake of two kinds of tracers in animal model;3,Probing a optimal imaging choice to delineate gross tumor volume?GTV?by comparing MRI?CT?¹⁸F-FLT PET/CT?¹⁸F-FDG PET/CT with pathological specimens;4,By the standard of pathological tumor specimens and nasopharyngeal tumor target delineated based on the MRI images,exploring the best SUV threshold of¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT to delineate nasopharyngeal tumor target;5,The optimal imaging method to determine the properties of lymphonodus will be explored by the comparison of pathological specimens,MRI,CT,¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT.Methods: The construction of rabbit VX2 nasopharyngeal transplanted tumor model: Firstly,The New Zealand white rabbits after anesthesia were fixed supinely.then selection of hyoid midpoint as the puncture point,Vaccination in the nasopharynx withprepared VX2 tumor tissue suspension under the guidance of CT.One week after the vaccination,observing the rabbits by CT each week,the model was established successfully when CT found the nasopharyngeal neoplasm;2,The image of FLT and FDG in malignant tumors: Injection of ¹⁸F-FLT into ear margin of model rabbit,60 min later,detection of the largest SUV value of interesting region.Then detection of the largest SUV value of ¹⁸F-FDG PET/CT as the same,and analysis of the imaging characteristics of FLT by comparing the largest SUV value of the two tracers;3,Exploring the best SUV threshold of ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT to delineate nasopharyngeal GTV and probing a optimal imaging choice to delineate tumor target: The CT?MRI?¹⁸F-FLT PET/CT ? ¹⁸F-FDG PET/CT have to be accomplished in 96 hours after the successful of modeling and measuring the volume of the tumor Immediately.Then respectively By the standard of gross volume,maximum diameter and maximum width measured from pathological tumor specimens and nasopharyngeal GTV delineated based on the MRI images,exploring the best SUV threshold of ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT to delineate nasopharyngeal GTV by comparing the gross volume,maximum diameter and maximum width of nasopharyngeal tumor target delineated based on ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT with the two standards.Finally,at the condition of the optimal SUV threshold,probing a optimal imaging choice to delineate GTV by comparing MRI ? CT ? ¹⁸F-FLT PET/CT ? ¹⁸F-FDG PET/CT with pathological specimens;4,The model rabbit who completed scan had receivedbilateral neck dissection,and Then all the dissected lymphonodus were examined by pathological staining to determine whether they were metastatic lymphonodus.The positive lymphonodus and negative lymphonodus shown on the MRI?¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT had been marked respectively,then the optimal imaging method to determine the properties of lymphonodus can be explored by the comparison of pathological specimens,MRI,CT,¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT.Results: 1,The success rate to establish VX2 nasopharyngeal transplanted tumor model by vaccination via hyoid midpoint is 89.47%?17/19?.lt is can be applied to follow-up study;2,The biological characteristics of rabbit VX2 nasopharyngeal transplanted tumor model which tumor growth rapid,invasion of parapharyngeal space,oropharynx and slope surrounding tissue,and cervical lymphonodus and pulmonary metastasis wil occurre at later period is similar to human nasopharyngeal squamous cell carcinoma;3,The uptake of ¹⁸F-FLT and¹⁸F-FDG is significantly increased in malignant tumors.The maximum SUV value of ¹⁸F-FDG PET/CT is 8.22±4.95?3.27¹1.06?,and the minimum SUV value is 3.43±1.7?2.13⁵.13?.The maximum SUV value of ¹⁸F-FLT PET/CT is0.66±0.57?1.23⁰.27?,and the minimum SUV value is 0.20±0.16?0.04⁰.35?;4,Gross volume comparison: The gross volume of pathological specimens?GTVp?is used as the standard:?1?¹⁸F-FDG PET/CT: The GTVFDG4.0 ?GTVFDG45% and GTVFDG50% delineated under the conditions of SUV4.0?SUV45%and SUV50% is compared with GTVp,the difference has no statisticallysignificant?P>0.05?.Among them,GTVFDG45% and GTVp are more close.?2?¹⁸F-FLT PET/CT:The GTVFLT0.6?GTVFLT55% and GTVFLT60% delineated under the conditions of SUV0.6,SUV55% and SUV60% is compared with GTVp,the difference has no statistically significant?P>0.05?.Among them,GTVFLT60%and GTVp are more close;?3?The GTVMRI and GTVCT is larger than GTVp,the difference has statistically significant?P<0.05?.?2?By the standard of GTVMRI:¹⁸F-FDG PET/CT:?1?The GTVFDG3.5 and GTVFDG35% delineated under the conditions of SUV3.5 and SUV35% is compared with GTVMRI,the difference has no statistically significant?P>0.05?,Among them,GTVFDG35% and GTVMRI are more close.?2?¹⁸F-FLT PET/CT: The GTVFLT0.5 and GTVFLT50% delineated under the conditions of SUV0.5 and SUV50% is compared with GTVMRI,the difference has no statistically significant?P>0.05?,Among them,GTVFLT50%and GTVMRI are more close.?3?Then the GTVCT is compared with GTVMRI,the difference has no statistically significant?P>0.05?;5,The comparison of maximum diameter:?1?the maximum diameter of pathological specimens?Lp?was used as the standard:?1?¹⁸F-FDG PET/CT: The LFDG4.0 and LFDG45%delineated under the conditions of SUV4.0 and SUV45% is compared with LMRI,the difference has no statistically significant?P>0.05?.?2?¹⁸F-FLT PET/CT: The LFLT0.7 and LFLT60% delineated under the conditions of SUV0.7 and SUV60% is compared with Lp,the difference has no statistically significant?P>0.05?,Among them,LFLT60% and Lp are more close.?3?The LMRI and LCT is larger than Lp the difference has statistically significant?P<0.05?.?2?the maximumdiameter of tumor target delineated based on MRI?LMRI?was used as the standard:?1?¹⁸F-FDG PET/CT:The LFDG3.5,LFDG30% and LFDG35% delineated under the conditions of SUV3.5,SUV30% and SUV35% is compared with LMRI,the difference has no statistically significant?P>0.05?,Among them,LFDG30%,LFDG35% and LMRI are more close.?2?¹⁸F-FLT PET/CT:The LFLT0.5 and LFLT50%delineated under the conditions of SUV0.5 and SUV50% is compared with LMRI,the difference has no statistically significant?P>0.05?,Among them,LFLT0.5 and LMRI are more close.?3?Then the LCT is compared with LMRI,the difference has no statistically significant?P>0.05?;6,The comparison of maximum width:?1?the maximum width of pathological specimens?Wp?was used as the standard:?1?¹⁸F-FDG PET/CT: The WFDG45% delineated under the conditions of SUV45% is compared with GTVMRI,the difference has no statistically significant?P>0.05?.?2?¹⁸F-FLT PET/CT: The WFLT60% delineated under the conditions of SUV60% is compared with Wp,the difference has no statistically significant?P>0.05?,Among them,WFLT60% and Wp are more close.?3?The WMRI is smaller than Wp and the WCT is larger than Wp,the difference has statistically significant?P<0.05?.?2?the maximum with of tumor target delineated based on MRI?WMRI?was used as the standard:no matter ¹⁸F-FDG PET/CT or ¹⁸F-FLT PET/CT,The WFDG ? WFLT delineated under the conditions of any SUV is compared with WMRI,the difference has statistically significant?P<0.05?,Then the WCT is compared with WMRI,the difference has statistically significant?P>0.05?;7,The optimal SUV threshold:?1?The pathological specimens wasused as the standard:?1?¹⁸F-FDG PET/CT: The GTVFDG45%,LFDG45% and WFDG45% delineated under the conditions of SUV45% is compared with GTVp,Lp and Wp,the difference has no statistically significant?P>0.05?,suggesting that the GTV,maximum with and maximum diameter delineated based on ¹⁸F-FDG PET/CT of 45% SUVmax is basically the same as the solid tumor specimen.?2?¹⁸F-FLT PET/CT: The GTVFLT 60%,LFLT 60% delineated under the conditions of SUV60% is compared with GTVp,Lp the difference has no statistically significant?P>0.05?,suggesting that the tumor target delineated based on¹⁸F-FLT PET/CT of 60% SUVmax is basically the same as the solid tumor specimen.?2?The MRI was used as the standard:?1?¹⁸F-FDG PET/CT:The GTVFDG35% and LFDG35% is compared with WMRI and LMRI,the difference has no statistically significant?P>0.05?,but the WFDG45% is compared with WMRI,the difference has statistically significant?P<0.05?,The WFDG45% is larger than WMRI,The tumor target delineated based on ¹⁸F-FDG PET/CT of 35% SUVmax is basically the same as the MRI.?2?¹⁸F-FLT PET/CT:The GTVFLT 50% and LFLT 50%is compared with GTVMRI and LMRI,the difference has no statistically significant?P>0.05?,but the WFLT50% is compared with WMRI,the difference has statistically significant?P<0.05?,The WFLT50% is larger than WMRI,The tumor target delineated based on ¹⁸F-FDG PET/CT of 50% SUVmax is basically the same as the MRI.8,The comparison of tumor target under the condition of optimal SUV:?1?The pathological specimens was used as the standard: The the solid tumor specimen can be truly reflected by GTV,maximum with andmaximum diameter delineated based on ¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT,but the CT and MRI can't.?2?MRI was used as the standard:The GTV and maximum diameter delineated based on MRI can be truly reflected by ¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT,but the maximum with is larger than WMRI,in conclusion,The two methods are similar with MRI;9,Diagnosis of metastatic lymphonodus: The diagnosis of ¹⁸F-FDG PET/CT and pathological about cervical lymphonodus show a high correlation.The diagnosis of ¹⁸F-FLT PET/CT and pathological about cervical lymphonodus show a higher correlation than ¹⁸F-FDG PET/CT.The diagnosis of MRI and pathological about cervical lymphonodus show a lower correlation.At the same time,the sensitivity,specificity,positive predictive value and negative predictive value of¹⁸F-FLT PET/CT to diagnose positive lymphonodus are higher than ¹⁸F-FDG PET/CT and MRI.conclusions: 1,The results showed that the success rate was high and the model was stable and reliable,which is a good method to establish the VX2 animal model of nasopharyngeal carcinoma by means of the middle ear puncture inoculation;2,The histological and biological characteristics of rabbit VX2 nasopharyngeal xenograft model are very similar to those of human nasopharyngeal poorly differentiated squamous cell carcinoma,it can be used to simulate the occurrence and development of nasopharyngeal carcinoma in a body;3,Although the maximum SUV uptake value and the minimum SUV uptake value of ¹⁸F-FLT tumor region were significantly lower than that of¹⁸F-FDG,the specificity is stronger than that of ¹⁸F-FDG,and it was highlysensitive to the diagnosis of malignant tumors;4,By the standard of pathological specimens,comparison with the three indicators GTV,Lmax and Wmax,¹⁸F-FDG PET/CT with 45% SUVmax as the optimal threshold to delineate nasopharyngeal tumor target,while ¹⁸F-FLT PET/CT uses 60%SUVmax as the optimal threshold to delineate nasopharyngeal tumor target.based on the results of MRI,¹⁸F-FDG PET/CT with 35% SUVmax as the optimal threshold to delineate nasopharyngeal target while ¹⁸F-FLT PET/CT uses 50% SUVmax as the optimal threshold to delineate nasopharyngeal target;5,By the standard of pathological specimens,the various aspects of pathological specimens can be truly reflectet by the tumor target of ¹⁸F-FDG PET/CT and¹⁸F-FLT PET/CT.However,there is a big difference between solid tumors and the tumor target delineated based on CT and MRI.By the standard of MRI,the tumor target delineated based on ¹⁸F-FDG PET/CT,¹⁸F-FLT PET/CT and CT is similar to MRI,but through them,the tumour target of ¹⁸F-FDG PET/CT and¹⁸F-FLT PET/CT are more similar;6,The diagnosis of ¹⁸F-FDG PET/CT and pathological about cervical lymphonodus are similar,the accuracy is higher than the ¹⁸F-FDG PET/CT and MRI,the ¹⁸F-FLT PET/CT has more advantage in diagnosis of cervical lymphonodus.