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Objectives Pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP) are diseases with a highly analogous visual presentation that are difficult to distinguish by imaging. The purpose of this research was to create a radiomics-based prediction model using dual-time PET/CT imaging for the noninvasive classification of PDAC and AIP lesions. Methods This retrospective study was performed on 112 patients (48 patients with AIP and 64 patients with PDAC). All cases were confirmed by imaging and clinical follow-up, and/or pathology. A total of 502 radiomics features were extracted from the dual-time PET/CT images to develop a radiomics decision model. An additional 12 maximum intensity projection (MIP) features were also calculated to further improve the radiomics model. The optimal radiomics feature set was selected by support vector machine recursive feature elimination (SVM-RFE), and the final classifier was built using a linear SVM. The performance of the proposed dual-time model was evaluated using nested cross-validation for accuracy, sensitivity, specificity, and area under the curve (AUC). Results The final prediction model was developed from a combination of the SVM-RFE and linear SVM with the required quantitative features. The multimodal and multidimensional features performed well for classification (average AUC: 0.9668, accuracy: 89.91%, sensitivity: 85.31%, specificity: 96.04%). Conclusions The radiomics model based on 2-[ 18 F]fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG) PET/CT dual-time images provided promising performance for discriminating between patients with benign AIP and malignant PDAC lesions, which shows its potential for use as a diagnostic tool for clinical decision-making. Key Points • The clinical symptoms and imaging visual presentations of PDAC and AIP are highly similar, and accurate differentiation of PDAC and AIP lesions is difficult. • Radiomics features provided a potential noninvasive method for differentiation of AIP from PDAC. • The diagnostic performance of the proposed radiomics model indicates its potential to assist doctors in making treatment decisions .

PurposeTo explore a multidomain fusion model of radiomics and deep learning features based on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images to distinguish pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP), which could effectively improve the accuracy of diseases diagnosis.Materials and methodsThis retrospective study included 48 patients with AIP (mean age, 65 ± 12.0 years; range, 37–90 years) and 64 patients with PDAC patients (mean age, 66 ± 11.3 years; range, 32–88 years). Three different methods were discussed to identify PDAC and AIP based on 18F-FDG PET/CT images, including the radiomics model (RAD_model), the deep learning model (DL_model), and the multidomain fusion model (MF_model). We also compared the classification results of PET/CT, PET, and CT images in these three models. In addition, we explored the attributes of deep learning abstract features by analyzing the correlation between radiomics and deep learning features. Five-fold cross-validation was used to calculate receiver operating characteristic (ROC), area under the roc curve (AUC), accuracy (Acc), sensitivity (Sen), and specificity (Spe) to quantitatively evaluate the performance of different classification models.ResultsThe experimental results showed that the multidomain fusion model had the best comprehensive performance compared with radiomics and deep learning models, and the AUC, accuracy, sensitivity, specificity were 96.4% (95% CI 95.4–97.3%), 90.1% (95% CI 88.7–91.5%), 87.5% (95% CI 84.3–90.6%), and 93.0% (95% CI 90.3–95.6%), respectively. And our study proved that the multimodal features of PET/CT were superior to using either PET or CT features alone. First-order features of radiomics provided valuable complementary information for the deep learning model.ConclusionThe preliminary results of this paper demonstrated that our proposed multidomain fusion model fully exploits the value of radiomics and deep learning features based on 18F-FDG PET/CT images, which provided competitive accuracy for the discrimination of PDAC and AIP.

Patients with advanced hepatocellular carcinoma (HCC) have very limited treatment options, among which transarterial radioembolization (TARE) receives increasing attention, relying on its promising efficacy and fewer side effect. However, a bibliometric analysis of TARE for HCC is still lacking. This study employed bibliometric methods to analyze the related articles over the past three decades, and aimed to identify trends in clinical research comparing TARE to other treatments. Articles related with TARE for HCC were obtained from the Web of Science (WoS). After screening, the R package Bibliometrix was employed to explore the primary bibliometric characteristics. The number of publications was analyzed and mathematically fitted to a curve using Microsoft Excel 2021 and SPSS 25, and then was plotted in the graph using GraphPad Prism 8.0. VOSviewer, SCImago Graphica, and Pajek were utilized for the analysis of researchers' co-authorship, co-occurrence, and visualization. Keywords citation burst was detected by CiteSpace software. A total of 1,110 articles from 1993 to 2023 were included in our final analysis, among which the United States not only ranked the first in term of the number of published articles, also was at the forefront in other important indicators, including the total number of article citations and the average citation frequency. Riad Salem from Northwestern University, also being the organization with the greatest number of research papers, was the most active author and has published 96 papers. The keywords were classified into three clusters: Y microspheres for TARE, Basic research on TARE, and Clinical trial of TARE for HCC. Furthermore, we identified the most frequently cited keywords with strong citation bursts since 2020 were \"multicenter,\" \"overall survival\" and \"PET/CT.\" Our study employed a bibliometric approach to achieve the visualization research on TARE for HCC, and further revealed the trends and frontiers of TARE research, providing valuable information for researchers to identify the critical and persistent challenges and select potential partners in related area. Based on our analysis, future research focus include the clinical comparative studies on the effect of TARE and TACE combined with immunotherapies or targeted therapy, dosimetry, and personalized TARE therapy for HCC.

Background 18 F-FDG PET/CT could satisfactorily show pancreatic and extra-pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This study aimed to identify 18 F-FDG PET/CT findings that might differentiate AIP from PC. Methods FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed. Pancreatic and extra-pancreatic lesions related findings, including maximum standardized uptake values (SUVmax) and patterns of FDG uptake, were identified and compared. Results All 26 patients with AIP had increased pancreatic FDG uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax was significantly different between AIP and PC, both in early and delayed PET/CT scans ( p  < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683 (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP patients were higher compared with those of PC patients ( p  < 0.05). In males,an inverted “V” shaped high FDG uptake in the prostate was more frequent in AIP than PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra-pancreatic bile duct was present in 4/26 of AIP patients, while was observed in none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG accumulation and increased inverted “V” shaped FDG uptake in the prostate could be found simultaneously. Conclusions 18 F-FDG PET/CT findings might help differentiate AIP from PC.

Purpose We aimed to analyze the change of quantitative intra-tumoral metabolic heterogeneity consisting of texture features and conventional metabolic parameters of pancreatic cancer (PC) in dual-time 2-deoxy-2( 18 F) fluoro- d -glucose ( 18 F-FDG) positron emission tomography-computed tomography (PET/CT). Methods A retrospective analysis was conducted considering the texture features and conventional metabolic parameters in dual-time 18 F-FDG PET/CT scans of PC patients. Features were extracted based on spatial distribution of 18 F-FDG uptake in image. Firstly, the texture features and the conventional metabolic parameters of the delayed scan were both compared with that of the early scan. Statistically different data was defined among them. Secondly, the study evaluated the correlations between retention index (RI) of the texture features and the conventional metabolic parameters. Finally, the variation of texture features in dual-time PET/CT of resectable PC patients and unresectable PC patients was calculated separately. Results In total, 183 PC patients were analyzed retrospectively in this research. The conventional metabolic parameters were all statistically different between the early and delayed scans except for metabolic tumor volume (MTV). In the radiomics, there were 59 textural features. Nineteen of 59 texture features were statistically different between the early and delayed scans. Features that were more than 10% different during two scans were observed in a substantial percentage of patients. Weak correlations were only found between MTV, TLG (Total lesion glycolysis), SUVpeak and the RI of some texture features in early or delayed scans. There were obviously fewer features with significant difference in resectable PC group than in unresectable PC group. Most features showing the difference in unresectable group while no significant difference in resectable group. Conclusions This study investigated the change and inner correlations of quantitative tumoral metabolic heterogeneity in the dual-time 18 F-FDG-PET/CT scan of PC patients. Some features displayed the difference between dual-time scans. Conventional metabolic parameters were weakly related to the change of texture feature. The change of texture feature in resectable PC group was different from that in unresectable PC group. This result is potential to provide more information for the image evaluation of PC.

Purposes Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131 I-FAP-2286 in pancreatic cancer. Methods Human pancreatic cancer PANC-1 cells were exposed to 131 I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131 I-FAP-2286 and 131 I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131 I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18 F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues. Results 131 I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131 I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131 I-FAP-2286 can target the tumor effectively. According to 18 F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, 131 I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled 131 I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth. Conclusions 131 I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.

Positron emission tomography (PET) has been proven as an important technology to detect the expression of programmed death ligand 1 (PD-L1) non-invasively and in real time. As a PD-L1 inhibitor, small peptide WL12 has shown great potential in serving as a targeting molecule to guide PD-L1 blockade therapy in clinic. In this study, WL12 was modified with HBED-CC to label 68Ga in a modified procedure, and the biologic properties were evaluated in vitro and in vivo. 68Ga-HBED-CC-WL12 showed good stability in saline and can specifically target PD-L1-positive cells U87MG and PANC02. In PANC02-bearing mice, 68Ga-HBED-CC-WL12 showed fast permeation in subcutaneous tumors within 20 min (SUVmax 0.37) and was of higher uptake in 90 min (SUVmax 0.38). When compared with 18F-FDG, 68Ga-FAPI-04, and 68Ga-RGD, 68Ga-HBED-CC-WL12 also demonstrated great image quality and advantages in evaluating immune microenvironment. This study modified the 68Ga-labeling procedure of WL12 and obtained better biologic properties and further manifested the clinical potential of 68Ga-HBED-CC-WL12 for PET imaging and guiding for immunotherapy.

•We have successfully developed a novel SPECT ligand 123/125I-AD-DRK for cheaper diagnostic nuclear medicine imaging of AD and/or non-AD tauopathies.•123/125I-AD-DRK can bind to amyloid and tau aggregates deposited in postmortem brains from the patients with AD and PSP, respectively.•123/125I-AD-DRK can visualize mature amyloid and tau aggregates in the living brains of APP23 and rTg4510 mice, respectively. Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK (123/125I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau.

68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT has been widely used in the diagnosis of prostate cancer (PCa); however, the urine lead shielding resulting from the urinary metabolism of tracers may obstruct the detection of surrounding metastasis. In this research, the additive value of super early scanning in diagnosing primary lesions and metastasis in the pelvic cavity was evaluated. Firstly, the differentiation efficiency of 68Ga-PSMA-11 PET scanned at 3 min post-injection (min P.I.) was measured in PSMA-positive (22rv1 cells) and PSMA-negative (PC3 cells) model mice. Secondly, 106 patients were scanned at 3 min P.I. for the pelvic cavity and then scanned as a standard protocol at 45 min P.I. In the results, the differential diagnosis of PSMA expression was completely reflected as early as 3 min P.I. for mice models. For patients, when correlated with the Gleason score, the quantitative results of the super early scan displayed a comparable correlation coefficient with the routine scan. The target to bladder ratios increased from 1.44 ± 2.40 at 45 min to 10.10 ± 19.10 at 3 min (p < 0.001) for the primary lesions, and it increased from 0.99 ± 1.88 to 9.27 ± 23.03 for metastasis. Meanwhile, the target to background ratios increased from 2.21 ± 2.44 at 3 min to 19.13 ± 23.93 at 45 min (p < 0.001) for the primary lesions, and it increased from 1.68 ± 2.71 to 12.04 ± 18.73 (p < 0.001) for metastasis. In conclusion, super early scanning of 68Ga-PSMA-11 PET/CT added referable information for metastasis detection in order to avoid disturbing tracer activity in the urinary system.

Transarterial radioembolization (TARE) with β-emitting radionuclides is widely used for hepatocellular carcinoma (HCC), but its clinical efficacy remains to be further improved. α-particle-emitting radionuclides possess high linear energy transfer (LET) and unique advantages in cancer therapy, motivating α-particle based composite platform. Accordingly, we engineer the first clinically mimetic α-TARE microsphere by in-situ ²²³Ra-doped calcium–alginate composite microsphere (²²³Ra/Ca-ALG MS) using a hydrogel matrix, in which alginate “egg-box” coordination captures Ra²⁺ to provide stable radiolabeling, delivered via selective hepatic arterial injection to HCC. The microspheres exhibited excellent radiolabeling stability (88% retention after 384 h) and potent, dose-dependent cytotoxicity against HCC cells under hypoxia. In an orthotopic rat HCC model, 223 Ra/Ca-ALG MS-based TARE achieves precise intratumoral localization and sustained retention on SPECT/CT; ¹⁸F-FDG PET/CT and histopathology indicate a robust antitumor response, while serum biochemistry and histology support a favorable safety profile. Moreover, ²²³Ra/Ca-ALG MS provide powerful immune-activating capacity. Transcriptomics reveals activation of DNA-damage response, immunogenic cell death, and antigen-presentation pathways, flow cytometry and immunohistochemistry show increased dendritic-cell maturation and CD8⁺ T-cell infiltration. Collectively, 223 Ra/Ca-ALG MS demonstrates hypoxia-tolerant cytotoxicity, immune-activating potential, offering new insights for the development of immune-based TARE strategies in HCC and showing promising prospects for clinical translation. Graphical abstract