Objective:To assess the diagnostic utility of ultrasound-guided fine-needle aspiration (FNA) combined with BRAF V600E gene mutation detection for discerning benign from malignant thyroid isthmus nodules classified as thyroid imaging report and data system (TI-RADS) 4a and 4b. Methods:A retrospective analysis was conducted on the clinical data of 48 patients with thyroid nodules of TI-RADS 4, who underwent surgical confirmation and pathological diagnosis at Jiaozuo People's Hospital between October 2019 and June 2022. Using surgical and pathological outcomes as the gold standard, the diagnostic efficacy of FNA cytopathology, BRAF V600E gene mutation detection, and the combined approach were individually evaluated for benign and malignant thyroid nodules of TI-RADS 4. Results:The receiver operating characteristic curve analysis revealed the diagnostic values of FNA, BRAF V600E gene mutation detection, and their combined use in predicting the benignancy or malignancy of thyroid isthmus nodules. For TI-RADS 4a nodules, the areas under the curves were 0.876 for FNA, 0.852 for BRAF V600E gene mutation detection, and 0.952 for the combined approach. For TI-RADS 4b nodules, the areas under the curves were 0.850, 0.858, and 0.908, respectively. The P-values were 0.010, 0.016, and 0.002 for TI-RADS 4a nodules, and 0.006, 0.005, and 0.001 for TI-RADS 4b nodules. Notably, the combined approach demonstrated larger areas under the curves compared with individual applications. Conclusion:The combined use of FNA and BRAF V600E gene mutation detection enhances the diagnostic accuracy for thyroid isthmus nodules classified as TI-RADS 4a and 4b, as reflected by an increased area under the receiver operating characteristic curve.

Objective:To explore whether multi-parametric MRI (mpMRI) combined with 68Ga-prostate specific membrane antigen (PSMA) PET/CT can improve the detection efficiency of clinically significant prostate cancer (csPCa). Methods:Clinical and imaging data of 152 patients (age (68.5±8.5) years) who underwent mpMRI and 68Ga-PSMA PET/CT examination for suspected prostate cancer in the First Affiliated Hospital of the Air Force Medical University from January 2021 to November 2022 were retrospectively analyzed, with the histopathological results from transrectal ultrasound guided biopsy as reference. Lesions with Gleason scores (GS) ≥3+ 4 from the biopsy were diagnosed with csPCa, and lesions with negative biopsy or GS 6 were diagnosed with non-csPCa. MpMRI was evaluated independently by two radiologists according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The radioactive uptake of 68Ga-PSMA PET/CT in prostate lesions was evaluated by SUV max. The independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences between the two groups, and then multivariate logistic regression analysis was performed. ROC curves analysis was used to analyze the diagnostic efficacies of individual and combined factors and Delong test was used. Results:There were 85 csPCa and 67 non-csPCa confirmed. Prostate specific antigen (PSA), PI-RADS score and SUV max were significantly different between the csPCa group and the non-csPCa group ( χ2=68.06, U values: -7.66, -8.98, all P<0.001). Multivariate logistic regression analysis indicated that PI-RADS score (odds ratio ( OR)=3.424, 95% CI: 1.651-7.100) and SUV max ( OR=1.931, 95% CI: 1.403-2.658) were independent predictors of csPCa (both P<0.001). ROC curves analysis revealed that the cut-off value for diagnosing csPCa was 4 for PI-RADS score and 5.6 for SUV max. The accuracy of mpMRI and PET/CT alone in csPCa diagnosis was 80%(122/152) (AUC of 0.789(95% CI: 0.711-0.866) with the sensitivity and specificity of 91%(77/85) and 67%(45/67)), and 87%(132/152) (AUC of 0.876(95% CI: 0.817-0.936) with the sensitivity and specificity of 81%(69/85) and 94%(63/67)), respectively. Several joint models incorporating 68Ga-PSMA PET/CT with mpMRI data were investigated, the model of PI-RADS 5 or PI-RADS 3-4 and SUV max>5.6 showed better performance than mpMRI and PET/CT alone and other joint models ( z values: 2.01-3.64, all P<0.05), with the accuracy of 91%(138/152) (AUC of 0.910(95% CI: 0.857-0.962) with the sensitivity and specificity of 89%(76/85) and 93%(62/67)). Conclusion:MpMRI combined with 68Ga-PSMA PET/CT can significantly improve the detection efficiency of csPCa, with the principal effect being improved in risk stratification of PI-RADS 3-4 lesions in mpMRI.

Objective:To explore the uptake characteristics and temporal changes of 68Ga-fibroblast activation protein inhibitors (FAPIs) and 18F-FDG in the anastomotic site of reconstructed digestive tracts after radical surgery for gastrointestinal adenocarcinoma. Methods:A cohort of 43 patients (28 males, 15 females; age range 28-79 years) who underwent radical surgery for gastrointestinal adenocarcinoma and underwent 18F-FDG PET/CT follow-up between November 2020 and June 2022 in the First Affiliated Hospital of the Air Force Medical University was prospectively included. One week after the 18F-FDG PET/CT examination, 68Ga-FAPI-04 PET/CT imaging was performed. ROIs were drawn on the PET images at the highest uptake level of anastomotic sites of reconstructed digestive tract and abdominal wall incisions, and SUV max and target-to-background ratio (TBR) were determined. χ2 test, one-way analysis of variance, Kruskal-Wallis rank sum test (Bonferroni correction) and Wilcoxon signed-rank test were supplied. Results:There were 86 surgical wounds (13 gastric-intestinal anastomotic sites, 14 esophagus-intestinal anastomotic sites, 16 intestinal-intestinal anastomotic sites, and 43 abdominal wall incisions) included. In 68Ga-FAPI-04 PET imaging, SUV max of gastric-intestinal anastomotic sites was higher than that of abdominal wall incisions, with a statistically significant difference (adjusted P=0.014). The TBR did not show statistically significant differences among different types of surgical wounds ( H=3.88, P=0.275). In 18F-FDG PET imaging, SUV max of gastric-intestinal, esophagus-intestinal, and intestinal-intestinal anastomotic sites were all higher than that of abdominal wall incisions, with statistically significant differences (adjusted all P<0.001). There were no statistically significant differences in TBR among different types of surgical wounds ( H=3.02, P=0.388). In 68Ga-FAPI-04 PET imaging, the TBR of all types of anastomotic sites exhibited a decreasing trend with increasing postoperative time. Except for intestinal-intestinal anastomotic sites, the differences in TBR between < 0.5-year and ≥ 1.5-year groups were statistically significant for other types of surgical wounds (adjusted P<0.05). In 18F-FDG PET imaging, the TBR of abdominal wall incisions showed a decreasing trend with increasing postoperative time. However, the TBR of other types of surgical wounds did not show a decreasing trend, and the differences in TBR among different time groups were not statistically significant ( H values: 0.53-2.75, P values: 0.252-0.768). In comparing the two PET imaging agents, for all surgical wounds within the <0.5-year and 0.5-1.5-year groups, the 68Ga-FAPI-04 TBR was consistently higher than the 18F-FDG TBR ( z values: -3.17 and -2.55, P values: 0.002 and 0.011). However, in the ≥1.5-year group, the TBR values tended to be consistent, and the differences were not statistically significant ( z=-0.70, P=0.485). Conclusions:The 18F-FDG uptake in the anastomotic sites of reconstructed digestive tracts reaches a low level under half a year after surgery and does not significantly change over time, while the 68Ga-FAPIs uptake remains relatively high within the first 1.5 years after surgery but decreases over time. These patterns suggest that clinical attention should be paid to the differential diagnosis of anastomotic inflammation or fibrosis, which resulting in agent uptake and local tumor recurrence.

Objective:To exploring the uptake of fibroblast activation protein (FAP) inhibitor (FAPI) in pancreatic cancer through 68Ga-FAPI-04 PET/CT imaging, and provide a basis for the FAP-targeted imaging of pancreatic cancer. Methods:Pancreatic cancer-patient-derived tumor xenograft (PDX) mouse models ( n=8) were developed, then 68Ga-FAPI-04 and 18F-FDG microPET/CT imaging were performed (4 in each group). The differences of percentage activity of injection dose per gram of tissue (%ID/g) of 68Ga-FAPI-04 and 18F-FDG were analyzed by independent-sample t test. 68Ga-FAPI-04 and 18F-FDG PET/CT imaging were performed in 5 patients (4 males, 1 female, age: 46-74 (63.0±11.9) years) with pancreatic cancer, and the maximum standardized uptake value (SUV max) of 68Ga-FAPI-04 and 18F-FDG in primary pancreatic cancer and the SUV max ratio of liver metastases to liver tissue were compared by paired t test. Results:MicroPET/CT imaging showed that 68Ga-FAPI-04 was obviously uptaken at all time points in the tumor of PDX mice. The uptake of 68Ga-FAPI-04 in PDX mice 60 min after injection was significantly higher than that of 18F-FDG ((6.58±0.44) and (4.29±0.13) %ID/g; t=4.152, P=0.008 9). PET/CT showed that the SUV max of 68Ga-FAPI-04 in pancreatic cancer was significantly higher than that of 18F-FDG (16.82±3.08 and 5.14±2.20; t=6.893, P=0.000 1) and the SUV max ratio of liver metastases to liver tissue of 68Ga-FAPI-04 was also significantly higher than that of 18F-FDG (4.57±1.47 and 1.30±0.16; t=3.803, P=0.019 1). Conclusion:68Ga-FAPI-04 can be highly uptaken in pancreatic cancer, suggesting that FAP can be a potential target for PET/CT imaging of pancreatic cancer.

Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake, in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells, and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo microPET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g, remarkably higher compared to (0.73±0.26) %ID/g of 18F-FDG uptake (t=8.826, P<0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16, which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors, the uptakes of 68Ga-NGR and 18F-FDG were both high, and the values were (2.46±0.23) %ID/g, (3.47±0.31) %ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors: (0.67±0.20) %ID/g vs (3.17±0.29) %ID/g;t=4.221, P<0.01.Western blot and immunohistostaining results were as follows: HT-1080(CD13+, G6Pase-), SMMC-7721(CD13+, G6Pase+), HT-29(CD13-, G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice, therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore, because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase, there is an underlying potential for molecular imaging in the determination of molecular phenotypes.

Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake,in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells,and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) ％ID/g,remarkably higher compared to (0.73±0.26) ％ID/g of 18F-FDG uptake (t =8.826,P＜0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16,which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors,the uptakes of 68 Ga-NGR and 18F-FDG were both high,and the values were (2.46±0.23) ％ID/g,(3.47±0.31) ％ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors:(0.67±0.20) ％ID/g vs (3.17±0.29) ％ID/g;t=4.221,P＜0.01.Western blot and immunohistostaining results were as follows:HT-1080(CD13+,G6Pase-),SMMC-7721(CD13+,G6Pase+),HT-29 (CD13-,G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice,therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore,because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase,there is an underlying potential for molecular imaging in the determination of molecular phenotypes.

Objective To explore the optimal conditions of preparing 68Ga-DOTA-iNGR (NGR peptide containing CendR motif),to evaluate its biodistribution in normal mice and to perform microPET imaging in tumor-bearing nude mice.Methods 68Ga fresh eluent (200 μl,92.5-129.5 MBq) obtaining with 68Ge-68Ga radionuclide generator was used to label DOTA-iNGR.The optimal conditions of labeling including pH,temperature,reacting time and concentration of DOTA-iNGR were determined.Then,the in vitro and in vivo stability and octanol/water partition coefficient of 68Ga-DOTA-iNGR were further analyzed.The biodistribution in normal Kunming mice was examined at 10,20,40,60 and 120 min after injection of 68Ga-DOTA-iNGR.Nude mice bearing HT-1080 (CDl3-positive) and HT-29 (CDl3-negative) tumors were established and underwent microPET imaging at 1 h after the intravenous injection of 68Ga-DOTA-iNGR.Data were analyzed using independent-sample t test.Results The optimal conditions of labeling was mixing 2 μg DOTA-iNGR peptide with 200 μl 68Ga (92.5-129.5 MBq) at pH 4.0,temperature 90-100 ℃ for 5-10 min.Under this condition,labeling rate reached (97.5± 1.3)％.The radiochemical purity of 68Ga-DOTA-iNGR in both saline (room temperature) and mouse serum (37 C) were both above 95％ after 4 h incubation,and the radiochemical purity in urine was greater than 85％ after 1 h metabolism in vivo.The partition coefficient was-2.71±0.18.In normal mice,majority of 68Ga-DOTA-iNGR was excreted from kidneys with a rapid clearance from blood.The in vivo microPET imaging showed that 68Ga-DOTA-iNGR was remarkably accumulated in the CD13-positive HT-1080 tumor.Conclusions Labeling DOTA-iNGR with 68Ga under our condition is a simple and efficient procedure with high labeling rate and high specificity.The product 68Ga-DOTA-iNGR has high stability,ideal biodistribution,and specific binding to CD13-positive tumor,which means that it's a very promising molecular probe for noninvasively detecting CD13-positive tumor.