Objective:To explore the effects of anlotinib on the proliferation, apoptosis, and migration of thyroid cancer cells, and investigate its role in inducing redifferentiation and enhancing iodine uptake capacity, providing a preliminary evaluation of its efficacy in tumor treatment.Methods:(1)The cell proliferation was detected by cell counting kit-8 (CCK-8) assay, and different concentrations (0, 1/4 half maximal inhibitory concentration (IC 50), 1/2IC 50, IC 50) of anlotinib were used to treat CAL62 and FTC133 thyroid cancer cells for 24h. The clonogenic formation experiment, cellular activity and drug toxicity staining, scratch healing assay, and apoptosis in situ fluorescence staining were employed to assess cell clonogenicity, apoptosis, and migration abilities. (2) CAL62 and FTC133 cells were treated with various concentrations of anlotinib, and changes in the expression levels of iodine metabolism-related proteins (sodium/iodide symporter (NIS), thyroid peroxidase (TPO), and thyroid-stimulating hormone receptor (TSHR)) were detected using Western blot. (3) Iodine uptake experiments were conducted to observe changes in the iodine uptake functionality of thyroid cancer cells following treatment with different concentrations of anlotinib for 24 h. (4) The thyroid cancer xenograft nude mouse models were established and divided into control group (physiological saline), low-dose group (1mg/kg), medium-dose group (2mg/kg), and high-dose group (4mg/kg). Mice were treated with varying doses of the drug, the therapeutic effects and the changes in iodine harvesting function on tumors were evaluated. One-way analysis of variance was used for comparison among groups. Results:Anlotinib treatment resulted in significantly reduced cell viability, decreased clonogenic formation, increased apoptosis rates, and reduced scratch healing rates in CAL62 and FTC133 cells ( F values: 53.75-211.90, all P<0.001). After anlotinib treatment, the levels of iodine metabolism-related proteins (NIS, TPO and TSHR) significantly increased ( F values: 21.14-710.00, all P<0.001), and iodine uptake rates in thyroid cancer cells also increased significantly ( F values: 36.45, 32.34, both P<0.001). The nude mouse treatment experiment showed tumor growth in the anlotinib treatment group was inhibited, and tumors iodine uptake rates were increased, both were statistically significant ( F values: 74.09, 38.22, both P<0.001). Conclusions:Anlotinib can inhibit thyroid cancer proliferation and growth, promote apoptosis, reduce cell migration capabilities, induce thyroid cancer cells redifferentiation, and enhance iodine uptake capacity. Anlotinib can induce the redifferentiation of thyroid cancer at the animal level and has better efficacy.

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

Objective:To explore the impact of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/tumor protein 53 (TP53) expression on the 68Ga-prostate specific membrane antigen (PSMA)-11 and 18F-FDG molecular imaging phenotypes in primary prostate cancer. Methods:A retrospective study was conducted on 75 prostate cancer patients (age (67.9±6.3) years) who received both 68Ga-PSMA-11 and 18F-FDG PET/CT imaging on initial diagnosis and subsequent radical prostatectomy at Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, between Auguest 2018 and July 2022. The correlation between PTEN and TP53 expression in prostate cancer and molecular imaging phenotype was analyzed by χ2 test, Kruskal-Wallis rank sum test and Bonferroni method based on the uptake of imaging agents in primary lesions and the results of immunohistochemical analysis of surgical specimens. Results:In prostate cancer tissues with PTEN expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 14/14 and 11/14, with the SUV max of 7.70(6.15, 11.05) and 15.55(6.75, 23.49) respectively. In prostate cancer tissues with TP53 expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 10/10 and 6/10, with the SUV max of 7.70(6.95, 8.05) and 9.50(5.38, 19.89) respectively. In prostate cancer tissues with different expression patterns of PTEN and TP53, there were significant differences in the positive rates of 18F-FDG uptake ( χ2=20.45, P< 0.001), 68Ga-PSMA-11 uptake ( χ2=14.97, P=0.002), and the SUV max of 68Ga-PSMA-11 uptake ( H=9.62, P=0.022). Additionally, patients with concurrent loss of PTEN and TP53 expression in the primary tumor had significantly lower SUV max of 68Ga-PSMA-11 uptake compared to those with expression of both PTEN and TP53 (5.70(4.40, 11.70) vs 20.95(13.73, 37.58); P=0.003 (Bonferroni method corrected)). Conclusion:PTEN/TP53 expression is associated with the 68Ga-PSMA-11 and 18F-FDG molecular imaging phenotype in primary prostate cancer.

In recent years, fibroblast activation protein inhibitor (FAPI) PET imaging, which targets the tumor microenvironment, has shown significant potential in evaluating solid tumors. Particularly, studies have demonstrated the value of 68Ga-FAPI PET in evaluation of gastric and colorectal cancer. This article reviews previous studies and provides an overview of how 68Ga-FAPI PET can be used in the diagnosis, staging, recurrence monitoring, clinical management, efficacy evaluation, and prognostic prediction of gastric and colorectal cancer, in order to provide a basis for the further utilization of this novel imaging agent, 68Ga-FAPI, in gastric and colorectal cancer.

Objective:To investigate the prognostic value of 18F-FDG PET/CT-based habitat radiomics combined with stacking ensemble learning model in overall survival (OS) of patients with hepatocellular carcinoma (HCC). Methods:A total of 136 HCC patients (114 males, 22 females, age (55.3±10.4) years) who underwent 18F-FDG PET/CT before treatment between January 2018 and January 2023 were retrospectively analyzed. Eighty-five cases from Tianjin First Central Hospital and 51 cases from Tianjin Medical University Cancer Institute and Hospital were used as a training cohort and an external validation cohort, respectively. The tumor volume of interest (VOI) was delineated on PET and CT images, and a total of 4 habitats were segmented by using the Otsu algorithm, including PET high ∩ CT low, PET low ∩ CT low, PET high ∩ CT high, and PET low ∩ CT high. After the feature selection, a total of 36 stacking ensemble learning models were established, and the optimal model was selected based on the calculated concordance index (C-index). Moreover, a combined model was developed by integrating the optimal model with clinical information. The predictive efficacy of those models was assessed by time-dependent ROC curves. Results:The model based on PET high ∩ CT high habitat radiomics features with multilayer perceptron (MLP) classifier had the highest C-index (0.770) in the external validation cohort, and it was regarded as the optimal radiomics model. The combined model incorporating this model with clinical information achieved an improved C-index of 0.815 in the external validation cohort. The combined model outperformed the other models for OS prediction, with a time-dependent AUC of 0.919, 0.900, and 0.862 in predicting the 1-year, 2-year, and 3-year OS, respectively. Conclusions:18F-FDG PET/CT-based habitat analysis outperforms traditional radiomics in OS prediction for HCC patients. By integrating the optimal habitat model with the clinical model, the combined model is able to improve the predictive efficacy.

Objective:To evaluate the value of deep-inhaled breath-hold (DIBH)-30s scanning with total-body PET/CT under half-dose injection mode in improving the poor alignment of thoracic and upper abdominal tumors.Methods:Forty-six patients (28 males, 18 females, age (57.3±11.4) years) who underwent half-dose 18F-FDG total-body DIBH-30s PET/CT examination because of suspect or confirmed thoracic and upper abdominal tumors in Sun Yat-Sen University Cancer Center between October 2022 and February 2023 were analyzed retrospectively. SUV, standard deviation (SD) and signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in free breath (FB)-8min, FB-30s and DIBH-30s PET images were measured; SUV of lesions, metabolic tumor volume (MTV) and tumor-to-background ratio (TBR) in DIBH-30s and FB-8min images were also measured; maximum diameter of contraposition offset and offset rate in coronal, transverse and sagittal directions of lesions in DIBH-30s and FB-8min images were calculated. Five-point Likert scale was used to score the overall image quality, image noise level and diagnostic confidence of fused images. Kruskal-Wallis rank sum test, Nemenyi test or Mann-Whitney U test was used to compare the parameters of different groups. Results:Among the 46 patients, 38 successfully completed breath-holding collection, and 80 lesions were detected, including 37 in the lungs and 43 in the livers. The liver SUV max (3.40(3.15, 3.63), 3.44(3.06, 3.70)) and SD (0.36(0.32, 0.41), 0.35(0.30, 0.40)) in DIBH-30s group and FB-30s group were higher than those (SUV max: 2.73(2.45, 2.92), SD: 0.15(0.13, 0.17)) in FB-8min group ( H values: 49.79, 85.27, χ2 values: 3.26-3.65, all P<0.001). The SUV max and the SD of mediastinal blood pool in DIBH-30s group and FB-30s group were also higher ( H values: 9.31, 59.73, χ2 values: 2.13-2.75, all P<0.01), while SNR liver and SNR med in those 2 groups were lower ( H values: 87.90, 54.11, χ2 values: 3.36-5.47, all P<0.001). The image noise scores of DIBH-30s group and FB-30s group were lower than the score of FB-8min group (3(3, 3) vs 3(3, 4) vs 5(5, 5); H=93.02, χ2 values: 2.13, 2.23, all P<0.001). The overall image quality score and diagnostic confidence score of DIBH-30s group were higher than those of FB-30s group and FB-8min group ( H values: 70.13, 24.22, χ2 values: 2.11-2.48, all P<0.001). The SUV and TBR of lesions in DIBH-30s group were higher than those of FB-8min group ( Z values: from -3.82 to -2.44, all P<0.05), while the MTV, contraposition offset and offset rate were lower than those of FB-8min group ( Z values: from -6.20 to -3.18, all P<0.001). Conclusions:DIBH-30s scanning with total-body PET/CT can make the focus alignment more accurate, which is suitable for short-time collection or low drug administration activity. It has a unique value in improving the poor focus alignment of chest and upper abdomen tumors.

Objective:To investigate the effects of 177Lu-prostate specific membrane antigen (PSMA)-I&T combined with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor (PARPi) fluzoparib on the proliferation and migration of prostate cancer cells and the tumor inhibitory effects. Methods:177Lu-PSMA-I&T was synthesized. Cytotoxicity assay, colony formation assay, 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation assay, Transwell cell migration assay, and terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, flow cytometry were performed to detect apoptosis and cell cycles. 22RV1 tumor-bearing mice models ( n=16) were established, and were randomly divided into 4 groups: control group (no treatment; n=4), fluzoparib monotherapy group (6mg/kg; n=4), 177Lu-PSMA-I&T monotherapy group (14.8MBq; n=4) and combination group (14.8MBq 177Lu-PSMA-I&T+ 6mg/kg fluzoparib; n=4). All mice were treated for 14 d. Tumor volume and body mass changes of tumor-bearing mice were observed and recorded. After the treatment, 18F-FDG PET/CT was performed to evaluate the tumor′s uptake of 18F-FDG. Effects of 177Lu-PSMA-I&T combined with fluzoparib on cell and tumor-bearing mice were observed. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:At half maximal inhibitory concentrations (IC 50) of 177Lu-PSMA-I&T (13.06MBq/ml) and fluzoparib (72.13μmol/L), compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment significantly enhanced the anti-tumor effect on 22RV1 cells, inhibited the DNA synthesis rate and colony-forming ability of 22RV1 cells, reduced cell migration rate, increased the percentage of DNA damage, resulted in a higher proportion of cells arrested in the G2/M phase and increased the apoptosis rate ( F values: 9.77-162.20, t values: 2.98-21.60, all P<0.05). Compared to the fluzoparib monotherapy group and the 177Lu-PSMA-I&T monotherapy group, the combination treatment resulted in a significant reduction in relative tumor volume (RTV%) 14 d post-administration and markedly decreased 18F-FDG uptake ( F values: 25.28 and 67.42, t values: 4.64-8.61, P values: 0.001-0.009). Conclusion:The combination of 177Lu-PSMA-I&T and fluzoparib can inhibit prostate cancer cell proliferation and migration, suppress tumor growth and metabolism, and demonstrates synergistic effects more effectively.

Objective:To conduct enrichment and biological behavior studies on CD44 + CD24 - triple-negative breast cancer (TNBC) stem-like cells, and to construct 68Ga-labeled CD44 peptide ( 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44p) and evaluate its targeting ability towards the surface marker CD44 of TNBC stem-like cells. Methods:Suspension sphere culture method was utilized to enrich and cultivate CD44 + CD24 - cell subpopulations from TNBC cell line MDA-MB-231 and non-TNBC cell line MCF-7. Flow cytometry was used to detect the expression of stem cell markers of different groups, cell scratch assay was performed to assess the migration ability of CD44 + CD24 - cell subpopulations, and Transwell invasion assay was performed to evaluate the invasion ability of CD44 + CD24 - cell subpopulations. 68Ga-NOTA-CD44p was prepared, followed by purification and identification with high-performance liquid chromatography (HPLC). The targeting ability of 68Ga-NOTA-CD44p towards CD44 + TNBC cells was evaluated through cellular uptake and blocking experiments. Data were analyzed by independent-sample t test, one-way analysis of variance and the least significant difference t test. Results:Suspension sphere culture successfully enriched CD44 + CD24 - TNBC stem-like cell spheres. Compared to the non-TNBC cell line MCF-7, TNBC cell line MDA-MB-231 exhibited better sphere-forming ability (18.50±3.73 vs 31.83±4.92; t=5.29, P<0.001) and a higher proportion of CD44 + CD24 - cell subset ((24.97±8.12)% vs (90.93±4.46)%; F=170.10, t=14.93, both P<0.001). The wound healing rate ((71.00±11.00)% vs (28.33±4.16)%; F=42.91, t=8.02, both P<0.001) and invasion rate ((60.60±16.87)% vs (24.16±8.15)%; F=11.83, t=4.40, both P<0.01) of CD44 + CD24 - MDA-MB-231 group cells were significantly increased compared to the CD44 + CD24 - MCF-7 group. MDA-MB-231 cells showed strong uptake ability of 68Ga-NOTA-CD44p, which decreased after CD44p blocking. Conclusions:Compared to CD44 + CD24 - MCF-7 cells, CD44 + CD24 - MDA-MB-231 cells exhibit higher malignant biological behavior. 68Ga-NOTA-CD44p targets the surface marker CD44 of TNBC stem-like cells, laying the research foundation for targeted therapy against TNBC with tumor stem cells as targets.

Objective:To investigate the application of 18F-FDG PET/MR and its derived parameters in the diagnosis and staging of bladder cancer. Methods:Forty patients (32 males, 8 females; age (66.8±11.2) years) with suspected bladder cancer between December 2019 and March 2022 were retrospectively included and underwent 18F-FDG PET/MR in Nanjing First Hospital. Parameters including SUV max, SUV mean, maximum tumor diameter and mean of apparent diffusion coefficient (ADC mean) were obtained, and bladder cancer muscle invasiveness and lymph node involvement were determined. The efficacy of 18F-FDG PET/MR and its derived parameters for tumor diagnosis and staging was analyzed using transurethral resection of bladder tumor (TUR-BT) or radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND) histopathology as the " gold standard". Independent-sample t test, Mann-Whitney U test or χ2 test was used to analyze the data, and Delong test was used to compare different AUCs. Results:Of 40 patients, 8 were non-muscle invasive bladder cancer (NMIBC), 32 were muscle invasive bladder cancer (MIBC), and 5 were pathologically confirmed to have lymph node metastasis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 18F-FDG PET/MR for identifying MIBC were 96.9%(31/32), 7/8, 96.9%(31/32), 7/8, 95.0%(38/40), respectively, and those for lymph node metastasis were 4/5, 90.0%(18/20), 4/6, 18/19, 88.0%(22/25), respectively. For pathological tumor (pT) staging, significant differences were observed between pT2-3 and pT1 groups in maximum tumor diameter ( t=-2.37, P=0.024), SUV mean( Z=-2.11, P=0.035), and ADC mean( t=2.91, P=0.006). The AUCs of maximum tumor diameter, SUV mean and ADC mean in distinguishing MIBC were 0.781, 0.746, and 0.825, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI alone in identifying MIBC were 87.5%(28/32), 1/8, 80.0%(28/35), 1/5 and 72.5%(29/40), respectively, with the AUC of 0.500. The AUC of 18F-FDG PET/MR in identifying MIBC was 0.796, which was better than MRI alone ( Z=5.54, P<0.001), and the accuracy of PET/MR was also higher than MRI alone ( χ2=7.44, P=0.006). Conclusion:Compared with MRI alone, 18F-FDG PET/MR significantly improves the diagnostic efficacy of bladder cancer and the accuracy of pT staging.

Objective:To analyze the clinical value of translocator protein (TSPO, 18kDa) radiotracer 18F- N, N-diethyl-2-(2-(4-(2-fluoroethoxy)-phenyl)-5, 7-dimethyl-pyrazolo[1, 5-a]pyrimidin-3-yl)-acetamide (DPA-714) PET/MR imaging for precise localization of epileptogenic zone in patients with drug-resistant epilepsy. Methods:From December 2022 to October 2023, 24 refractory epilepsy patients (12 males and 12 females, age (27.5±8.1) years) who underwent surgery in Xuanwu Hospital, Capital Medical University were retrospectively enrolled. All patients received hybrid 18F-DPA-714 PET/MR before surgery, with the surgical resection site and stereoelectroencephalography recordings of the seizure focus serving as the gold standard. Initial qualitative analysis of the images was performed, followed by semi-quantitative analysis using the ROI method to calculate the asymmetry index (AI) of the proposed epileptogenic zone, assessing the degree of increased abnormal uptake (area with AI>10% was considered as the epileptogenic zone). Follow-up assessment using the Engel classification was conducted at least one year postoperatively. Differences of lesion detection efficiency of conventional MRI and PET/MR were evaluated using McNemar test. Results:Among 24 enrolled patients, 13 cases (54.2%) showed positive findings on conventional MRI, while 21 cases (87.5%) exhibited single or multiple foci of abnormally increased tracer uptake on PET/MR imaging, indicating an improved lesion detection rate ( χ2=4.90, P=0.021). Of the MRI-positive patients, 12/13 also had positive findings on PET/MR, with a localization accuracy of 10/13. Among the MRI-negative patients, 9/11 showed positive PET/MR findings, with a localization accuracy of 6/11. At one year post-surgery, 75.0%(18/24) of patients had a favorable outcome (Engel Ⅰ). Conclusion:18F-DPA-714 PET/MR imaging can accurately locate epileptogenic foci, especially for MRI-negative lesions, providing reliable information for surgical planning to improve postoperative outcomes.