Chemical Synthesis Of FDG, FLT And The Relevance Studied Of Differential Diagnosis In The Pulmonary Nodules

PrefaceConcept of the positive Positron emission computer tomography(PET)is utilizing positron emission radioactive nuclide and labeled chemical compounds enter human body to visualization partly or whole body,PET can detect topography of positive electron radiates in the organism noninvasively,it can reflect variation in physiology, pathology,biochemistry,metabolism,It can distinguish benign tumor and malignant tumor and play important role on the stages and grouping of tumor,tumour biology behavioral assessment,respects of the monitoring,and play important role on post-treatment response.PET make imaging diagnostics developed from the anatomic form to combination of anatomic form and biological chemistry form rapidly,and adapt to needs of diagnosis and therapy on disease in molecule level.2-[fluorine 18]fluoro-2-deoxy-d-glucose(FDG)is tracer agent general used in clinical research.The cells have glucose utilization due to upregulation of hexokinase activity Glucose is taken up by tumor cells by facilitated transport(via glucose transporters[GLUT])and then undergoes glycolysis with the formation of pyruvate under aerobic conditions.However,under hypoxic conditions,glucose is metabolized under anaerobic conditions with resultant increased tumor lactate levels.FDG is a radiopharmaceutical analog of glucose that is taken up by metabolically active tumor cells using facilitated transport similar to that used by glucose.The rate of uptake of FDG by the tumor cells is proportional to their metabolic activity,especially the pace of the anaerobic glycolysis is faster than normal cells.Like glucose,it undergoes phosphorylation to form FDG-6-phosphate;however,unlike glucose,it does not undergo further metabolism,thereby becoming trapped in metabolically active cells.But FDG can also be absorbed in inflammation cells,granulation tissue,etc.,existence of false positive is certain.The nucleoside analogue 3'-deoxy-3'-¹8F-fluorothymidine(FLT)has recently been introduced for imaging cell proliferation has been developed rapidly at present,¹8F-FLT is monophosphorylated by thymidine kinasel,which leads to intracellular trapping. Since the TK1 concentration is especially increased during the S phase of the cell cycle, the uptake of ¹8F-FLT is believed to depend on proliferation,thus specifically diagnose the cell hyperplasia with fast tumour is a foundation of development of tumour,closely related with biological behaviors such as the growth,infiltrating,recurrence,metabasis and prognosis of tumour.PurposeThe aims of studies is to develop the new synthesis ¹8F-FDG,¹8F-FLT method used ionic liquid(IL)as Phase Transfer Catalyst(PTC),meantime we hope to understand the influence of the synthesis rate of tracer on two kinds of radioactivity different substrate quality,under complex reaction time and different heating temperature condition at the same time,and compare it with routine synthesis on advantage and deficiency.The aims of clinical studies is to discuss the value of semi-quantitive index-standardized uptake value(SUV)of ¹8F-FLT PET and ¹8F-FDG PET used to differential lung nodules.Materials and methodsTo separate 18F ionic transferred from cyclotron first,We Study ¹8F-FDG productivity with the difference volume(K₂CO₃,IL,acetonitrile)used 1,3,4,6-tetra-O-acetyl-2-O-trifluromethanesulfonyl-D-mannopyanose(TATM)25mg precursor and 1-Butyl-3-methylimidazolium trifluoromethanesulfonate(BMI)as Phase Transfer Catalyst(PTC).To separate 18F ionic transferred from cyclotron first,We study ¹8F-FLT productivity with the different K₂CO₃ volume,heat temperature and precursor quantity used 3-N-tert-Butoxycarbonyl-(5'-O-(4,4'-dimethoxytripphenylmethyl)-2'-deoxy- 3'-O-(4-ni trobenzenesulfonyl)-β-D-threopentofuranosyl)thymine as precursor and BMI as Phase Transfer Catalyst(PTC). In clinical study,the muliti-center clinical trial about ¹8F-FLT and ¹8F-FDG PET-CT imaging from Apr 2005 to Mar 2007 with six medical centers 95 patients, finally,55 patients(22women,33men,17-82 years old,mean age of 53.3±17.1year) were enrolled in this reseach.Every patient got definite diagnosis from pathological analysis or close follow-up.Tumoral uptake was determined by visual assessment and calculation of standardized uptake value(SUV).All images of PET were evaluated by five experienced nuclear medicine physician used blind method.To two being apparent to carry on vision analyze and half quantitative analysis separately as PET result of pharmaceutical,among them FDG standard adopts malignant SUV＞2.5;Absorb＞2.0, FLT standard adopts malignant SUV＞1.35;Absorb＞1.0.Resultwe got the highest ¹8F-FDG productivity(55%)and radiochemistry purity(93%) with 0.2ml K₂CO₃,0.3ml BMI,0.7ml acetonitrile and TATM 25mg.we can get the highest productivity of ¹8F-FLT syntheses with 0.1ml 1M,130°and 30mg precursor.We found 16 malignant and 39 benign lesions.Treat the pathological or follow-up results as the"golden standard ",the sensitivity,specificity,accuracy of FDG-PET(cut off=2.5)alone of diagnosis of lung cancer were 93.75%,25.64%,45.45%, respectively,and the corresponding data of FLT-PET(cutoff=1.35)alone of diagnosis of lung cancer were 93.75%,41.03%,56.36%,respectively;additionally,with the method of double-blind and group-evaluating,the sensitivity,specificity,accuracy of FDG in diagnosing lung cancer were 87.5%,58.97%,67.27%,the corresponding data of FLT were 68.75%,76.92%,74.55%;the corresponding data of combination of FDG and FLT were 81.25%,87.18%,85.45%,respectively.(3)The areas under the ROC curves were 0.744 for FDG-PET(p＜0.05)and 0.788 for FLT-PET(p＜0.05).(4)In all 55 patients,The FLT uptake was correlated moderately with the FDG uptake(r=0.614, p=0.000).Conclusionwe can got the highest 18F-FDG productivity used BMI as PTC with TATM precursor. BMI IL can been used PTC to synthesis 18F-FLT which have higher productivity, high stability and quickly.The diagnostic ability of FLT-PET is superior to that of FDG-PET.The sensitivity of FDG-PET is higher than that of FLT-PET but the specificity of former is lower than that of the later for diagnosis of lung cancer,and the combination of them may increase the specificity.Furthermore,FLT uptake was found to correlate with FDG uptake.