The Experimental Studies And Preliminary Clinical Application Of ¹⁸F-FLT Applied For Non-small Cell Lung Cancer

Objective To investigate the binding characteristics of ¹⁸F-FDG or ¹⁸F-FLT before and after administrated with Gemcitabine in human non-small cell lung cancer cell A549 as well as the preliminary linical applications of ¹⁸F-FLT,in order to observe the value of the PET imaging agent ¹⁸F-FLT in the diagnosis and follow up of non-small cell lung cancer.Methods (1) The binding rates of ¹⁸F-FDG or ¹⁸F-FLT were measured under different conditions: 5×10⁴～5×10⁶cells, 1.85～29.6KBq ¹⁸F-FDG or ¹⁸F-FLT , 0～11.1mmol/L glucose levels, and 20～120min to measure;(2) MTT was ultilized to measure the inhibitory rate on A549 cell with different dose of Gemcitabine at 24h;24 hours after administrated with Gemcitabine(5～120mmol/L), the binding inhibitory rate of ¹⁸F-FDG and ¹⁸F-FLT were detected. (3) ¹⁸F-FLT PET/CT imaging was performed in 10 patients and 7 patients with non-small cell lung cancer who were certified by histopathology both performed ¹⁸F-FDG and ¹⁸F-FLT PET/CT imaging ( one poorly differentiated adenocarcinoma,three poorly differentiated squamous cancers,one mucous adenocarcinoma,one Large cell carcinoma). one case of lung cancer postoperative bone metastasis,one patient of Laryngeal cancer with lung inflammation,and one patient who was certified inflammation after treatment. The positive focus of infection and its SUVmax was analyzed.Results (1) The binding rates of ¹⁸F-FDG were(3.00±0.22)%,(3.63±1.05)%,(7.84±4.47)%,(31.91±4.14)%,(33.6±13.75)%,while it of ¹⁸F-FLT were (6.34±1.04)%,(7.11±1.90)%,(13.63±0.50)%,(16.0±5.02)%,(20.60±1.10)% at the condition of cells desity ranges from 5×10⁴ to 5×10⁶ per flask;The binding rate of ¹⁸F-FDG were (14.21±3.71)%,(18.55±3.76)%,(27.38±1.60)%,(28.37±4.63)%,(31.91±4.14) %,(32.67±10.49)%,while ¹⁸F-FLT were (10.4±1.46)%,(11.65±1.03)%,(13.74±1.43)%,(14.3±1.83)%,(16.0±5.02)%,(21.49±2.67)% respectively, at the condition of 1×10⁶cells, incubating time from 20 to 120 minutes ;at the condition of 1×10⁶cells, incubating time 100 minutes ,radioactivity ranges from 1.85 to 29.6 KBq ,The binding rate of ¹⁸F-FDG and ¹⁸F -FLT were (34.91±7.16)%,(31.91±4.14)%,(33.35±5.54)%,(35.68±8.92)%,(34.28±3.31)% and(13.69±4.09)%,(16.0±5.02)%,(16.02±4.73)%,(18.83±1.56)%,(16.51±2.02)% accordingly;at the condition of 1×10⁶cells, incubating time 100 minutes ,radioactivity 3.7 KBq ,glycose concentration from 0 to 11.1mmol/L ,The binding rates of ¹⁸F-FDG and ¹⁸F-FLT were (31.91±4.14)%,(6.34±1.70)%,(5.03±0.79)%,(3.56±0.68)%and(16.0±5.02)%,(15.20±1.34)%,(13.82±1.41)%,(13.91±1.14)% accordingly;(2) The inhibitory rate of A549 cell was (10.38±7.42)%,(11.25±6.70)%,(20.65±12.05)%,(56.71±34.07)%,(82.25±21.53)% and(95.75±4.03)% after administrated with Gemcitabine at the dose of 5,10,20,40,60,and 120 mmol/L respectively,it rised with the concentration of Gemcitabine increasing , which presented positive correlation(r=0.831,P<0.01); The binding inhibitory rate of ¹⁸F-FDG and ¹⁸F-FLT were(42.12±11.68)%,(60.99±10.76)%,(72.71±14.66)%,(75.73±10.51)%,(92.85±3.41)%,(95.36±3.74)%and(69.72±5.5)%,(66.81±4.19)%,(65.13±4.97)%,(69.73±5.90)%,(71.90±3.70)%,(73.94±3.78)% accordingly after administrated with Gemcitabine at the dose of 5,10,20,40,60,and 120 mmol/L respectively,which presented positive correlation too(r=0.75,P<0.01;r=0.50, P<0.01) (3)7 patients with non-small cell lung cancer wer all both positive in ¹⁸F-FDG and ¹⁸F-FLT PET/CT imaging. 19 lesions of non-small cell lung cancer were found out by ¹⁸F-FDG while ¹⁸F-FLT were 14. The SUVmax of ¹⁸F-FDG was from 2.49 to 12.41 and mean SUVmax was 6.41.while ¹⁸F-FLT was from 2.11 to 8.09 and mean SUVmax was 3.74.the sensitivity of ¹⁸F–FDG is higher than ¹⁸F-FLT ; the ¹⁸F–FDG PET/CT imagings of the two inflamation lessions were positive while negative of ¹⁸F–FLT,the specificity of ¹⁸F–FLT was higher than ¹⁸F–FDG.Conclusion (1) On certain conditions,¹⁸F-FDG and ¹⁸F-FLT uptake rates of A549 cells increased as the cell number and incubating time grew,irrelative with radioactivity, ¹⁸F-FDG uptake rates decreased when glycose concentration raised while ¹⁸F-FLT uptake rates were irrelative with glycose concentration; (2) The inhibitory rate of A549 cell rised with the concentration of Gemcitabine increasing, which presented positive correlation;¹⁸F-FDG and ¹⁸F-FLT binding inhibitory rates of A549 cells were positive relative with the MTT cell growing inhibitory rate(r=0.75,P<0.01;r=0.50,P<0.01); (3) the sensitivity of ¹⁸F–FDG is higher than ¹⁸F-FLT whihe the specificity of ¹⁸F–FLT was higher than ¹⁸F–FDG, the imaging quality of ¹⁸F-FLT was poorer than ¹⁸F-FDG generally.and the SUV of ¹⁸F-FLT was lower than ¹⁸F -FDG.