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Objective:To investigate predictive value of model based on pre-surgical 18F-FDG PET/CT metabolic parameters for mediastinal lymph node metastasis (LNM) in lung adenocarcinoma. Methods:A total of 288 patients with lung adenocarcinoma (135 males, 153 females, age (61.6±8.5) years) who diagnosed and treated in the Fourth Hospital of Hebei Medical University from January 2016 to February 2021 were enrolled retrospectively. All patients underwent 18F-FDG PET/CT examination within 1 month before operation, and underwent complete resection of primary lung tumor and standard lymph node dissection. PET/CT parameters were extracted (PET metabolic parameters: minimum SUV(SUV min), SUV max, SUV mean, SUV standard deviation (SUV std), metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT parameters: minimum CT value (HU min), maximum CT value (HU max), mean CT value (HU mean), CT value standard deviation (HU std)). Multivariate logistic regression analysis was used for screening parameters and establishing model to predict LNM. ROC curves analyses were used to evaluate the predictive performance of models. Results:Among 288 patients, 90 had LNM, and 361 metastatic lymph nodes (N1: 186, N2: 175) were reported by pathology. SUV min (odds ratio ( OR)=1.859, 95% CI: 1.074-3.220, P=0.027), SUV max ( OR=2.255, 95% CI: 1.306-3.893, P=0.004), SUV mean ( OR=0.277, 95% CI: 0.115-0.665, P=0.004) were predictors of LNM. The AUC of PET/CT model was 0.849 (95% CI: 0.804-0.893), and the sensitivity, specificity, accuracy, and positive and negative predictive values were 87.8%(79/90), 72.2%(143/198), 77.1%(222/288), 59.0%(79/134) and 92.9%(143/154), respectively. Conclusion:The model based on 18F-FDG PET/CT metabolic parameters can improve the accuracy of pre-surgical N-staging in patients with lung adenocarcinoma.
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Objective:To investigate the value of pre-therapy 18F-FDG PET/CT radiomic models in differentiating epidermal growth factor receptor (EGFR) exon 19 deletion from exon 21 L858R missense in patients with non-small cell lung cancer (NSCLC). Methods:A total of 172 patients with EGFR mutant NSCLC (54 males, 118 females, age: (56.2±12.5) years) in the Fourth Hospital of Hebei Medical University between January 2015 and November 2019 were retrospectively included. Exon 19 mutation was found in 75 patients and exon 21 mutation was identified in 97 patients. The patients were divided into training set ( n=121) and validation set ( n=51) in a 7∶3 ratio by using random number table. The LIFEx 4.00 package was used to extract texture features of PET/CT images of lesions. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature screening. Three machine learning models, namely logistic regression (LR), random forest (RF), and support vector machine (SVM) models, were constructed based on the selected optimal feature subsets. The ROC curve analysis was performed to assess the predictive performance of those models. Finally, decision curve analysis (DCA) was used to evaluate the clinical value of the models. Results:Nine radiomics features, including 6 PET features (histogram (HISTO)_Kurtosis, SHAPE_Sphericity, gray level run length matrix (GLRLM)_ low gray-level run emphasis (LGRE), GLRLM_ run length non-uniformity (RLNU), neighborhood grey level different matrix (NGLDM)_Contrast, gray level zone length matrix (GLZLM)_ short-zone low gray-level emphasis (SZLGE)), and 3 CT features (gray level co-occurrence matrix (GLCM)_Correlation, GLRLM_ run percentage (RP), NGLDM_Contrast), were screened by LASSO algorithm. Three machine learning models had similar predictive performance in the training and validation sets: AUCs for the RF model were 0.79, 0.77, and those for the SVM model were 0.76, 0.75, for the LR model were 0.77, 0.75. The DCA showed that the 3 machine learning models had good net benefits and clinical values in predicting EGFR mutation subtypes.Conclusion:18F-FDG PET/CT radiomics provide a non-invasive method for the identification of EGFR exon 19 deletion and exon 21 L858R missense mutations in patients with NSCLC, which may help the clinical decision-making and the formulation of individualized treatment plan.
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Objective To evaluate the clinical value of 18F-FDG PET/CT in the detection of residual,recurrent and metastatic diseases in post-treatment uterine cervical cancer patients presenting with elevated serum squamous cell carcinoma (SCC) antigen levels.Methods Between March 2009 and October 2012,18F-FDG PET/CT was performed in 48 patients(average age (47.5±11.2) years) with suspected residual,recurrent or metastatic uterine cervical cancer because of increased serum SCC antigen level (＞1.5 tμg/L).The final diagnosis was established by pathology or more than 1 year of clinical follow-up.The diagnostic efficiency of 18F-FDG PET/CT was calculated.Two-sample t test was used for data analysis.Results The serum SCC levels were 1.6-42.5(mean:8.6±9.4) μg/L.Among the 48 patients,45 (93.75％) were confirmed of having malignant lesions.18F-FDG PET/CT along with other imaging detected 174 lesions,of which 169 were proven as residual,recurrent or metastatic diseases.18F-FDG PET/CT correctly identified 159 lesions,yielding a diagnostic sensitivity and accuracy of 94.08％(159/169) and 91.38％(159/174),respectively.The diagnostic sensitivity and accuracy for residual and recurrent diseases were both 9/10;for lymph node metastasis were 94.59％ (105/111) and 92.92％ (105/113),respectively;and for other sites of metastasis were 93.75％ (45/48) and 88.24％ (45/51),respectively.There was no significant difference of SUVmax between the patients with residual/recurrent disease (mean:6.9±3.8,range:2.0-13.7) and those with metastasis (mean:6.3±2.7,range:2.0-14.4,t=0.629,P＞0.05).Conclusion 18F-FDG PET/CT is valuable for the detection of residual,recurrent and metastatic diseases in the uterine cervical cancer patients pr esenting with elevated serum squamous cell carcinoma antigen after conventional treatment.
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Objective To prepare the 99Tcm-labeled human epidermal growth factor receptor type 2 (HER2) affibody molecule ZHER2:342 and evaluate its receptor binding specificity in vitro.Methods The molecular ZHERa:342 was labeled with 99Tcm using the ligand exchange method.The labeling efficiency and radiochemical purity were measured by HPLC.The major factors,such as the mass of SnC12 and NaOH and reaction time were analyzed,and the optimal method was summarized.Cell binding kinetics and cellular retention of the probe were investigated in HER2-expressing SKOV-3 cells and MDA-MB-231 cells with low HER2 expression respectively.HER2 binding specificity of 99Tcm-ZHER2:342 was analyzed by a pre-injection of excess unlabeled ZHER2:342 to saturate HER2 receptors.One-way analysis of variance and two-sample t test were used.Results The optimal labeling procedure was as follows:5 μg (1 g/L) of ZHER2:342 was mixed with 5 μg of NaOH (1 g/L),then 8.8 μg SnC12(1 g/L,solution) was added,followed by 150 μl (37 MBq) 99TcmO4-solution,and finally the mixture was slightly vortexed and incubated for 1 h at room temperature.99TcmZHER2:342 was stable in vitro with a high labeling efficiency of (98.10± 1.73)％.The radiochemical purity was ＞ 98％,and was more than 85％ after the incubation for 24 h in saline and fresh human serum.The cell binding of 99Tcm-ZHER2:342 with HER2-expressing SKOV-3 cells gradually increased over time with a peak of (9.95± 1.02)％ at 6 h.The binding of 99Tcm-ZHER2:342 in SKOV-3 cells was significantly higher than that in MDA-MB-231 cells at every time point (5.68-9.88 vs 0.56-2.11 ; t:from-34.50 to-13.14,all P＜0.01).The labeled molecular probe retained the capacity to bind specifically to HER2-expressing SKOV-3 cells since the cell binding decreased from (9.95 ± 1.02) ％ to (2.11 ±0.27) ％ after receptor saturation (t =-13.14,P＜0.01).Conclusions 99Tcm-ZHER2:342 has a high labeling efficiency,good stability and optimal binding specificity.These characteristics enable it to be a promising molecular probe for HER2-targeting imaging.
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Objective To evaluate the in vitro effect on tumor cell uptake,tumor imaging and in vivo biodistribution of 99Tcm-epidermal growth factor receptor (EGFR) mRNA antisense PNA probe mediated by cationic liposome.Methods The oligonucleotide with sequence complementary to part of the EGFR mRNA antisense PNA was hybridized in an anti-parallel orientation targeted PNA.PNA hybridization complexes were labeled with 99Tcm by ligand exchange.The assembly of lipofectamine and 99Tcm-labeled heteroduplex was achieved by electrostatic interactions,and the radiolabeled purity was determined by reversedphase HPLC (RP-HPLC).The disparities of cell uptake in SKOV3 cells and the differences of biodistribution and molecular imaging in BALB/c nude mice bearing SKOV3 xenografts between lipofectanine-mediated 99Tcm-EGFR mRNA antisense PNA (group 1) and 99Tcm-EGFR mRNA antisense PNA (group 2) were analyzed.Two-sample t (or t') test and Wilcoxon rank sum test were used for statistical analysis.Results The labeling rates of both group 1 and group 2 were more than 95％ within 6 h.The cell uptake at 1,2,4,6,12,24 h after injection was (28.90±1.12)％,(32.76±1.20)％,(38.20±3.11)％,(41.23±1.60)％,(46.63±1.55)％ and (46.78±2.14)％ in group 1,and was (3.51±0.39)％,(3.90±0.40)％,(4.69±0.18)％,(5.91±0.26)％,(5.30±0.22)％ and (5.39±0.17)％ in group 2 respectively (t'=47.11-58.67,Z=2.80,all P＜0.05).The retention ratios showed significant difference between the two groups (t'=7.25-11.55,Z=2.80,all P＜0.05).The SKOV3 tumor could be visualized in both groups at 1 h post injection but much better visualized in group 1.The T/NT ratios were higher in group 1 at all time points (t =3.96,t'=12.65-14.69,Z=2.83-5.29,all P＜0.05).The T/NT ratios at uptake peak were 5.02 and 3.95,respectively.The probe accumulated mainly in tumor,kidneys and liver.Tumor uptake increased with time ((1.49±0.09) ％ID/g and (2.15±0.21) ％ID/g at 1 h,(3.90±0.65) ％ID/g and (5.00±0.10) ％ID/g at 6 h) after lipofectamine treatment.The ratios of tumor to contralateral muscle were also higher in group 1 (t =11.24,t' =3.96-11.94,all P＜0.05).Conclusions Lipofectamine-mediation can significantly improve the intracellular delivery of radionuclide molecular probe.Lipofectamine-mediated 99Tcm-EGFR mRNA antisense PNA can greatly improve imaging contrast and visualization of EGFR-over-expressing tumors.