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Purpose: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. Methods: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. Results: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. Conclusion: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a promising cancer treatment method. However, it has previously been centered on adjuvant therapy, often falling short as a preoperative treatment of solid cancers, largely attributed to the hypoxic and immunosuppressive microenvironments of untreated tumors. Herein, we develop a multifunctional nanoagent based on edge-oxidized graphene (EOG) for tumor imaging and neoadjuvant thermal immunotherapy. EOG, readily synthesized from selective oxidation and mechanical exfoliation of graphene flakes, exhibits good biocompatibility and remarkable microwave absorption capabilities owing to its large aromatic domains. Consequently, it has demonstrated utility in both microwave-induced thermoacoustic imaging and thermal therapy in a mouse hepatoma model. Furthermore, EOG-based thermal therapy is combined with immunotherapy, which can significantly reduce tumor volume and inhibit tumor growth. A mechanistic study reveals that microwave thermal energy alleviates tumor hypoxia, promotes immunogenic cell death, and ultimately enhances antitumor immune responses. This work pioneers a microwave-based imaging-guided immunotherapy strategy for neoadjuvant treatment of solid tumors and reveals the cell-level pathway of the involved immune suppression. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in the initial staging of patients with newly diagnosed nasopharyngeal carcinoma (NPC), compared with 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) PET/CT. Materials and Methods: Forty-seven treatment-naïve patients with newly diagnosed NPC underwent magnetic resonance imaging (MRI), [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT within 1 week. The diagnostic efficiency of all imaging modalities for evaluating primary tumour extension was compared from the two aspects of soft tissue and bony structure involvement. The accuracy of two PET/CT methods for diagnosing cervical lymph node (CLN) metastases was compared, and MRI served as the standard reference. T and N stages were assessed by MRI, [68Ga]Ga-FAPI PET/CT and [18F]F-FDG PET/CT. Immunohistochemical (IHC) staining for FAP was conducted in 22 of the patients. Results: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in the assessment of primary tumour invasion in the cavernous sinus (10 vs. 1, p < 0.001) and bony structures (207 vs. 177, p < 0.001). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated T stage in 13 and 2 patients, while [18F]F-FDG PET/CT upgraded and underestimated T stage in 5 and 13 patients. However, [68Ga]Ga-FAPI PET/CT was inferior to [18F]F-FDG PET/CT in diagnosing positive CLNs based on the analyses of patients, neck sides, neck levels and individual nodes. [68Ga]Ga-FAPI PET/CT changed therapeutic schedules in 8 patients because of stage group changes. The presence of FAP with high quantity and intensity in cancer-associated fibroblasts (CAFs) was confirmed in all tumour specimens. Conclusion: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in detecting the cavernous sinus and bony structure involvement of primary NPC tumours, suggesting its value in improving T staging and therapeutic regimen selection. However, the performance of [68Ga]Ga-FAPI PET/CT is less promising for N staging because it detected fewer positive CLNs than [18F]F-FDG PET/CT. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to characterize benign lesions showing increased 68Ga-FAPI-04 uptake on FAPI PET/CT.Methods: We retrospectively reviewed 182 patients with suspected various cancers who were performed 68Ga-FAPI-04 PET/CT imaging from August 2020 to December 2020. The diagnoses of the benign lesions were made by the CT findings (CT), other imaging information (OII) (contrast enhance CT, FDG PET, ultrasound, MRI or others), clinical information (CI) (medical history, laboratory examination, symptom, physical sign and follow-up information) or histological biopsy (HB).Results: A total of 185 primary malignant tumors were detected by FAPI PET/CT with the median SUVmax of 9.0 (range from 0.97 to 25.71). There were 360 benign lesions with increased FAPI uptake were detected in 146 (146/182, 80.2%) patients with the median SUVmax of 3.64 (range from 1.39 to 21.56), including inflammatory processes (n = 231, 64.2%), exostosis (n = 54, 15%), hemorrhoid (n = 47, 13.1%), fracture (n = 17, 4.7%), hepatic fibrosis (n = 4, 1.1%), and others (n = 7, 1.9%).Conclusion: Benign lesions with increased 68Ga-FAPI-04 uptake are common. The overall SUVmax of benign lesions is lower than that of malignant tumors, however there is a large overlap of SUVmax range. Similar to FDG PET, some benign lesions can be easily diagnosed by combining CT findings, special location and clinical data, but there are still some lesions that may be confused with malignant lesions, which need to be paid more attention.Trail Registration: NIH ClinicalTrials.gov (NCT04499365). [ABSTRACT FROM AUTHOR]

Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied to treat nasopharyngeal carcinoma (NPC). However, the molecular changes and functions of DDP in NPC chemo-resistance remain poorly understood. In the present study, transcriptomic sequencing between 5-8F and 5-8F/DDP cells was performed to identify differential expression and alternative splicing (AS) characteristics in DDP-resistant NPC cells. Transcriptomic profiling identified 1,757 upregulated genes and 1,473 downregulated differentially expressed genes (DEGs). Bioinformatic analysis revealed that these DEGs were associated with or participated in important biological regulatory functions in NPC. Validation of 20 significant DEGs using quantitative real-time reverse transcription PCR showed that the expression patterns of 17 mRNAs were in accordance with the sequencing data. Intron retention was identified as the major AS event in chemoresistant cells. Furthermore, the expression level of matrix metalloproteinase 1 (MMP1), which was one of the most upregulated mRNAs in the chemoresistant cell lines, was significantly associated with the migration, invasion, and proliferation of NPC cells in vitro. Our study revealed that dysregulated genes and AS-mediated DDP chemoresistance might play important roles in NPC development and progression. Targeting aberrantly expressed genes might clarify the pathogenesis of NPC and contribute to developing new therapeutic strategies for NPC. [ABSTRACT FROM AUTHOR]

In humans, zinc finger protein 671 (ZNF671) is a type of transcription factor. However, the contribution of tumor heterogeneity to the functional role of ZNF671 remains unknown. The present study aimed to determine the functional states of ZNF671 in cancer single cells based on single-cell sequencing datasets (scRNA-seq). We collected cancer-related ZNF671 scRNA-seq datasets and analyzed ZNF671 in the datasets. We evaluated 14 functional states of ZNF671 in cancers and performed ZNF671 expression and function state correlation analysis. We further applied t-distributed stochastic neighbor embedding to describe the distribution of cancer cells and to explore the functional state of ZNF671 in cancer subgroups. We found that ZNF671 was downregulated in eight cancer-related ZNF671 scRNA-seq datasets. Functional analysis identified that ZNF671 might play a tumor suppressor role in cancer. The heterogeneous functional states of cell subgroups and correlation analysis showed that ZNF671 played tumor suppressor roles in heterogeneous cancer cell populations. Western blot and transwell assays identified that ZNF671 inhibited EMT, migration, and invasion of CNS cancers, lung cancer, melanoma, and breast carcinoma in vitro. These results from cancer single-cell sequencing indicated that ZNF671 played a tumor suppressor role in multiple tumors and may provide us with new insights into the role of ZNF671 for cancer treatment. [ABSTRACT FROM AUTHOR]

Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. However, the methylation status, expression, and prognostic role of ZNF671 in solid tumors remain unclear. The aim of this study was to explore the relationship between ZNF671 and the prognosis of patients with solid tumors. We performed a pan-cancer analysis of the methylation status and mRNA and protein expression of ZNF671 using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. We further evaluated the prognostic value of ZNF671 expression among numerous cancer types using the "Kaplan–Meier plotter" (KM plotter) database. We found that downregulation of ZNF671 is associated with hypermethylation of its promoter. Survival analysis established that the downregulation of ZNF671 predicts poor prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) solid tumors. CCK-8 and Transwell functional assays showed that ZNF671 could inhibit tumor cell proliferation, migration, and invasion. These results indicate that ZNF671 is an excellent predictive factor for BRCA, CESC, HNSC, KIRP, LUAD, PAAD, SARC, and UCEC solid tumors and may play crucial roles in the development and progression of these tumors. [ABSTRACT FROM AUTHOR]

• [18F]FDG PET/CT has been proved as a valuable tool in detecting underlying malignancy in patients suspected of having a paraneoplastic syndrome. However, [18F]FDG PET/CT imaging in the diagnosing paraneoplastic dermatoses (PD) has not been clearly defined. • In our retrospective study of 60 patients with suspected PD, [18F]FDG PET/CT could identify the underlying neoplasms in 18/19 (94.7 %) PD patients and changed the clinical management in 9/19 (47.4 %) PD patients. • [18F]FDG PET/CT is a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients. We retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose ([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). From an institutional PET/CT database (2014–2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. We analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. This study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients. [ABSTRACT FROM AUTHOR]

Objective: Our study was designed to explore the utility of 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99mTc-3PRGD2 integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose (18F-FDG) metabolic imaging in a nude mouse model.Methods: 99mTc-3PRGD2 was synthesized using a HYNIC-3PRGD2 lyophilized kit with 99mTcO4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 107/ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99mTc-3PRGD2. Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99mTc-3PRGD2, to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99mTc-3PRGD2 and 37 MBq of 18F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99mTc-3PRGD2 and 18F-FDG.Results: The biodistribution study first validated that the tumour uptake of 99mTc-3PRGD2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99mTc-3PRGD2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99mTc-3PRGD2 integrin receptor imaging was more sensitive than 18F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of 99mTc-3PRGD2 was consistently higher than that of 18F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of 18F-FDG was higher than that of 99mTc-3PRGD2.Conclusion: Our study demonstrated that 99mTc-3PRGD2 is a valuable tumour molecular probe for the detection of early stage HCC compared with 18F-FDG, meriting further investigation of 99mTc-3PRGD2 as a novel SPECT tracer for tumour imaging. [ABSTRACT FROM AUTHOR]

Abstract: Ischemic colitis is the most common form of ischemic bowel disease; identification of ischemic colitis with PET/CT is rare. We present a case of unexplained ischemic colitis in a 66-year-old man who underwent 18 F-FDG PET/CT to exclude intestinal malignancy and was subsequently recruited in a clinical trial regarding 68 Ga-FAPI. 18 F-FDG PET/CT showed intense activity in the intestinal lumen where mucosa had chronic inflammation. Conversely, 68 Ga-FAPI PET/CT revealed high tracer uptake in the intestinal wall and adjacent mesentery. Our case showed the different distribution pattern of 18 F-FDG and 68 Ga-FAPI in ischemic colitis., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This study was supported in part by the Joint Funds for the Innovation of Science and Technology Fujian Province (no. 2021Y9134) and the Startup Fund for Scientific Research of Fujian Medical University (no. 2021QH1056)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 53-year-old man with newly diagnosed nasopharyngeal carcinoma (NPC) underwent 99m Tc-MDP bone scintigraphy for the potential bone metastases, and paired 68 Ga-DOTATATE and 68 Ga-FAPI PET/CT for initial staging. 68 Ga-DOTATATE PET/CT identified 2 abnormal foci with increased tracer uptake in the cervical vertebra and the ilium, whereas 68 Ga-FAPI PET/CT and bone scan detected only the ilium lesion. A subsequent biopsy confirmed NPC metastasis in the ilium. Furthermore, baseline and follow-up bone scintigraphy revealed that the positive lesion in the cervical vertebra, as indicated in 68 Ga-DOTATATE PET/CT, was also a bone metastasis. This case highlighted the potential superiority of 68 Ga-DOTATATE in NPC., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This study was funded by the Natural Science Foundation of Fujian Province (No. 2023J01564)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 28-year-old woman presented with abdominal pain, bowel dysfunction, and weight loss for 3 months. 18F-FDG PET/CT revealed multiple hypermetabolic lesions in the intestines and peritoneal thickening/caking with moderate FDG activity. 68Ga-FAPI PET/CT showed intense FAPI uptake in the aforementioned FDG-avid lesions and a larger number of abnormal foci with intense FAPI uptake in the peritoneum than that shown in 18F-FDG images. Endoscopy-guided biopsy from the colonic mucosa was consistent with tuberculosis. The positive findings of 68Ga-FAPI in the current case highlighted that 68Ga-FAPI may have value in the evaluation of intestinal tuberculosis., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflict of interest. This study was funded in part by the National Natural Science Foundation of China (81971651), the Natural Science Foundation of Fujian Province (2019J01454, 2020J05249), and the Fujian Provincial Health Commission Science and Technology and Programme (2020GGA045)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Whole brain radiotherapy has been a standard treatment of brain metastases. Stereotactic radiosurgery provides more focal and aggressive radiation and normal tissue sparing but worse local and distant control. This meta-analysis was performed to assess and compare the effectiveness of whole brain radiotherapy alone, stereotactic radiosurgery alone, and their combination in the treatment of brain metastases based on randomized controlled trial studies. Electronic databases (PubMed, MEDLINE, Embase, and Cochrane Library) were searched to identify randomized controlled trial studies that compared treatment outcome of whole brain radiotherapy and stereotactic radiosurgery. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were hazard ratios with 95% confidence intervals calculated for time-to-event data extracted from survival curves and local tumor control rate curves. Odds ratio with 95% confidence intervals were calculated for dichotomous data, while mean differences with 95% confidence intervals were calculated for continuous data. Fixed-effects or random-effects models were adopted according to heterogeneity. Five studies (n = 763) were included in this meta-analysis meeting the inclusion criteria. All the included studies were randomized controlled trials. The sample size ranged from 27 to 331. In total 202 (26%) patients with whole brain radiotherapy alone, 196 (26%) patients receiving stereotactic radiosurgery alone, and 365 (48%) patients were in whole brain radiotherapy plus stereotactic radiosurgery group. No significant survival benefit was observed for any treatment approach; hazard ratio was 1.19 (95% confidence interval: 0.96-1.43, p = 0.12) based on three randomized controlled trials for whole brain radiotherapy only compared to whole brain radiotherapy plus stereotactic radiosurgery and hazard ratio was 1.03 (95% confidence interval: 0.82-1.29, p = 0.81) for stereotactic radiosurgery only compared to combined approach. Local control was best achieved when whole brain radiotherapy was combined with stereotactic radiosurgery. Hazard ratio 2.05 (95% confidence interval: 1.36-3.09, p = 0.0006) and hazard ratio 1.84 (95% confidence interval: 1.26-2.70, p = 0.002) were obtained from comparing whole brain radiotherapy only and stereotactic radiosurgery only to whole brain radiotherapy + stereotactic radiosurgery, respectively. No difference in adverse events for treatment difference; odds ratio 1.16 (95% confidence interval: 0.77-1.76, p = 0.48) and odds ratio 0.92 (95% confidence interval: 0.59-1.42, p = 71) for whole brain radiotherapy + stereotactic radiosurgery versus whole brain radiotherapy only and whole brain radiotherapy + stereotactic radiosurgery versus stereotactic radiosurgery only, respectively. Adding stereotactic radiosurgery to whole brain radiotherapy provides better local control as compared to whole brain radiotherapy only and stereotactic radiosurgery only with no difference in radiation related toxicities.