| Tumor cells exhibit high FDG uptake because of their increased expression of glucose transporters and changes in the enzyme levels (low ratio of glucose-6-phosphatase /hexokinase). However, FDG is not a very tumor-specific substance and its accumulation in benign lesions with increased glucose metabolism may cause difficulty in correctly interpreting FDG imaging data. Therefore the investigation of more efficient methods using FDG for differentiation of malignant from benign lesions is warranted. The aim ofthis study was to evaluate the usefulness of dual time point ~18F-FDG coincidence SPECT imaging in differentiation of malignant from benign lesions.1. The experimental study of dual time point FDG imaging Objective To investigate the difference in the rates of FDG uptake between malignant and inflammatory cells and the manifestation of FDG imaging between tumor-bearing and inflammation-bearing animal model (C57 BL mice), in order to determine feasibility of FDG imaging with coincidence SPECT in separating malignant from benign lesions and to lay a foundation to future clinical study. Methods In vitro studies:(1)Attached malignant cell lines, which included mammary cancer (MCF7 and MDA231), gastric carcinoma (7901), SCLC(h446), hepatocarcinoma (C6),brain glioma (SHG4) were dissociated with 2.5% trypsin and then taken count of for experiment.(2)Human peripheral blood mononuclear cells were isolated from 6 healthy donors using Ficoll methods.(3)FDG was diluted in the burette which already contained 100μ L of cell suspension (5×10~5/L) to obtain a final concentration of 37KBq(1μCi)/10μL andthen incubated at 37V for 20 ~ 60min.(4)The cells were washed 4 times with phosphate-buffered solution. The radioactivity was measured by Y -counting.(5)After decay correction, the increased per centum was calculated between N2 ( 60 min) and Ni (20 min).Animal study:(1)20 normal C57 BL mice were divided into two groups randomly.(2)Lewis lung cancer cells were hypodermic injected into right axilla of group 1 named tumor group. After 2 weeks the mice can be prepared for imaging if the tumor sizes were larger than 2cm.(3)The mixture of talc powder and blanc fixe (2:1 )was implanted in the left flank of group 2 named inflammatory group. Four weeks later the mice were fit for imaging.(4)The animals were fasted for more than 6h and administered 4.81MBq/kg(130 u Ci/kg) intravenously.(5)Tumor group or inflammatory group was randomly divided into two groups, respectively. FDG imaging of each of these groups was obtained 45min or 90min after injection.(6)Regions of interest (ROI) were placed over the targets (T) and contra lateral background (B) on the coronal view, and then T/B value was calculated for both time points. Ttest was performed on the data with SPSS.Results(l)In vitro studiesAll malignant cells tested had increased FDG uptake over time, with an average increase of 39.46%. By contrast, FDG uptake in mononuclear cells tested decreased over time with an average decrease of 4.97%.(2)Animal studiesThe average T/B value of tumor-bearing animal model from early image was 2.11 ± 0.74, whereas that from delayed images was 2.78 ± 0.68. The T/B values from delayed images were significantly higher than those from early images (31.58% ± 5.84% of the early images; P = 0.000). By contrast, the average T/B value of inflammation-bearing animal model decreased over time(-6.09 ± 7.30%. P < 0.05). The average T/B ratio from image 1 was 1.40 ± 0.14, whereas the average T/B ratio from image 2 was 1.31 ± 0.11.Conclusions The malignant lesions(cells) have different degrees of increased FDG uptake over time, whereas inflammatory lesions(cells) have different degrees of decreased FDG uptake over time or remain stability. The ratio of T/B increased 30% over time was more likely to provide clinically relevant information.2. Clinical study of dual time point FDG imagingObjective To evaluate the clinical value of dual time point FDG coincidence SPECT imaging in differentiation of malignant from benign lesions.Methods(1) Seventy-two patients with known or suspected cancer or recurrence were evaluated in this study. All patients had fasted for at least 6 h and had blood sugar levels of 4.2 ~ 6.9mol/L before the 18F-FDG injection.(2) Data acquisition began 45 ~ 50min after the intravenous injection of 185 ~ 370 MBq FDG The intervals between the first time point and the second time point acquisition were 30 ~ 60min.(3) Regions of interest (ROI) were placed over the Targets (T) and contralateral background (B) on the coronal view, and then T/B value was calculated for both time points.Results(l)The average T/B ratio of the lesions in cancer patients increased from 3.61 ± 2.11at image 1 to 5.57 ± 3.15(.P = 0.000)at image 2(55.69% ± 26.93%, P = 0.000). By contrast, the average T/B ratio of benign lesions predominantly remained constant or declined slightly over time from 2.67 ±1.90 to 2.75 ±2.02 (1.12% ± 10.01%; P<0.05) .(2)When assessing the diagnostic value of the first emission image by applying a T/B value threshold of 2.0 for separating benign from malignant lesions, the sensitivity, specificity, accuracy and positive predictive value was 89.66%, 64.28%, 84.72%, 91.23% respectively. When the same T/B value threshold was applied to the data from the second images, the sensitivity increased to 96.55% and the accuracy and positive predictive value increased to 90.28%, 91.80% respectively. However, by adopting a T/B value increase of > 30% between the first and second images as a criterion for malignancy, the sensitivity, specificity, accuracy and positive predictive value increased to 98.28 %, 92.86%, 97.22%, 98.28% respectively.Conclusions Dual time point coincidence SPECT imaging is a simple and practical method fordifferentiating malignant from benign lesions, which can improve the sensitivity and specificity of coincidence SPECT imaging for detection of malignant tumors.
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