68 Ga-PSMA PET/CT in Hepatic Metastasis From Pancreatic Neuroendocrine Tumor.

ABSTRACT: A 53-year-old man underwent both 18 F-FDG and 68 Ga-PSMA PET/CT to evaluate a mass in the left upper abdomen. The scans demonstrated intense uptake of both 18 F-FDG and 68 Ga-PSMA in the mass. However, a nodule in the left lobe of the liver showed increased uptake of 68 Ga-PSMA, which was not FDG avid. Histopathological examination after surgical resection of the mass confirmed the diagnosis of pancreatic neuroendocrine tumor (G2). Subsequently, 68 Ga-DOTATATE PET/CT demonstrated intense radioactivity of the nodule in the left lobe of the liver consistent with hepatic metastasis from neuroendocrine tumor.

Inhibition of abnormal C/EBPß/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology.

Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs) in the brain. These LBs are primarily composed of α-Synuclein (α-Syn), which has aggregated. A recent report proposes that CCAAT/enhancer-binding proteins ß (C/EBPß) may act as an age-dependent transcription factor for α-Syn, thereby initiating PD pathologies by regulating its transcription. Potential therapeutic approaches to address PD could involve targeting the regulation of α-Syn by C/EBPß. This study has revealed that Nrf2, also known as nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), suppresses the transcription of C/EBPß in SH-SY5Y cells when treated with MPP+ . To activate Nrf2, sulforaphane, an Nrf2 activator, was administered. Additionally, C/EBPß was silenced using C/EBPß-DNA/RNA heteroduplex oligonucleotide (HDO). Both approaches successfully reduced abnormal α-Syn expression in primary neurons treated with MPP+ . Furthermore, sustained activation of Nrf2 via its activator or inhibition of C/EBPß using C/EBPß-HDO resulted in a reduction of aberrant α-Syn expression, thus leading to an improvement in the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) in mouse models induced by 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and those treated with preformed fibrils (PFFs). The data presented in this study illustrate that the activation of Nrf2 may provide a potential therapeutic strategy for PD by inhibiting the abnormal C/EBPß/α-Syn signaling pathway.

Head-to-Head Comparison of 68Ga-NODAGA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: Interim Analysis of a Prospective Bicenter Study.

The current study aimed to compare 68Ga-NODAGA-Cpa-cyclo(d-Cys-amino-Phe-hydroorotic acid-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)-d-Tyr-NH2 (JR11) and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: A prospective bicenter study aimed at enrolling 100 patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors was conducted. The first 48 patients represented the study cohort. Each patient received 68Ga-DOTATATE on the first day and 68Ga-NODAGA-JR11 on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection. Normal-organ uptake, lesion numbers, lesion uptake, and sensitivity were compared. The potential impact on clinical management was also determined. Results: Overall, 68Ga-NODAGA-JR11 demonstrated lower background uptake in normal organs. Compared with 68Ga-DOTATATE, 68Ga-NODAGA-JR11 detected significantly more liver lesions (673 vs. 584, P = 0.002). The target-to-background ratio of liver lesions was significantly higher on 68Ga-NODAGA-JR11 (6.4 ± 8.7 vs. 3.1 ±2.6, P = 0.000). Comparable uptake was observed for primary tumors, bone lesions, and lymph node metastases. In total, 180 lesions were detected on conventional imaging in 15 patients; 165 and 139 lesions of them were positive on 68Ga-NODAGA-JR11 and 68Ga-DOTATATE, leading to a sensitivity of 91.7% and 77.2%, respectively. In 14.5% (7/48) of patients, 68Ga-NODAGA-JR11 PET might have a potential impact on clinical management. Conclusion: 68Ga-NODAGA-JR11 shows better sensitivity and a higher target-to-background ratio than 68Ga-DOTATATE. The detection of more lesions by the antagonist may have a potential impact on clinical management in a subgroup of patients.

Recognizing pathology of renal tumor from macroscopic cross-section image by deep learning.

OBJECTIVES: This study aims to develop and evaluate the deep learning-based classification model for recognizing the pathology of renal tumor from macroscopic cross-section image. METHODS: A total of 467 pathology-confirmed patients who received radical nephrectomy or partial nephrectomy were retrospectively enrolled. The experiment of distinguishing malignant and benign renal tumor are conducted followed by performing the multi-subtypes classification models for recognizing four subtypes of benign tumor and four subtypes of malignant tumors, respectively. The classification models used the same backbone networks which are based on the convolutional neural network (CNN), including EfficientNet-B4, ResNet-18, and VGG-16. The performance of the classification models was evaluated by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Besides, we performed the quantitative comparison among these CNN models. RESULTS: For the model to differentiate the malignant tumor from the benign tumor, three CNN models all obtained relatively satisfactory performance and the highest AUC was achieved by the ResNet-18 model (AUC = 0.9226). There is not statistically significance between EfficientNet-B4 and ResNet-18 architectures and both of them are significantly statistically better than the VGG-16 model. The micro-averaged AUC, macro-averaged sensitivity, macro-averaged specificity, and micro-averaged accuracy for the VGG-16 model to distinguish the malignant tumor subtypes achieved 0.9398, 0.5774, 0.8660, and 0.7917, respectively. The performance of the EfficientNet-B4 is not better than that of VGG-16 in terms of micro-averaged AUC except for other metrics. For the models to recognize the benign tumor subtypes, the EfficientNet-B4 ranked the best performance, but had no significantly statistical difference with other two models with respect to micro-averaged AUC. CONCLUSIONS: The classification results were relatively satisfactory, which showed the potential for clinical application when analyzing the renal tumor macroscopic cross-section images. Automatically distinguishing the malignant tumor from benign tumor and identifying the subtypes pathology of renal tumor could make the patient-management process more efficient.

[68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of gastric cancer: comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to compare the performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the evaluation of primary and metastatic lesions of gastric cancer. METHODS: Fifty-six patients with histologically proven gastric carcinomas were enrolled in this study, including 45 patients for staging and 11 patients for restaging after surgery. Each patient underwent both [18F]FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. The activity of tracer accumulation in lesions was assessed by maximum standardized uptake value (SUVmax) and TBR (lesions SUVmax/ascending aorta SUVmean). Histological workup served as a standard of reference. If tissue diagnosis was not applicable, the follow-up data including the results of laboratory tests and medical imaging could also serve as a reference. RESULTS: [68Ga]Ga-DOTA-FAPI-04 PET/CT was comparable to [18F]FDG on detecting primary tumors and lymph node (LN) metastases, whereas [68Ga]Ga-DOTA-FAPI-04 outperformed [18F]FDG in detecting peritoneal (159 vs. 47, P < 0.001) and bone metastases (64 vs. 55, P = 0.003) by the lesion-based analysis. [68Ga]Ga-DOTA-FAPI-04 showed higher SUVmax (10.3 vs. 8.1, P = 0.004) and TBR (11.6 vs. 5.8, P < 0.001) in primary tumor, and higher TBR in LN involvement (8.0 vs. 3.7, P < 0.001) and peritoneal metastases (8.1 vs. 3.2, P < 0.001), compared with [18F]FDG PET/CT. The specificity and positive predictive value of [68 Ga]Ga-DOTA-FAPI-04 were significantly higher than that of [18F]FDG (100.0% vs. 97.7%, P < 0.001; 100.0% vs. 57.1%, P = 0.001) in determining the LN status. [68Ga]Ga-DOTA-FAPI-04 was comparable to [18F]FDG in evaluating N-staging (47.1% vs. 23.5%, P = 0.282). [68Ga]Ga-DOTA-FAPI-04 PET/CT detected more positive recurrent lesions in all restaging patients and showed clearer tumor delineation. Two patients underwent follow-up [68Ga]Ga-DOTA-FAPI-04 PET/CT scans after chemotherapy, which both showed remission. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/CT can better evaluate primary gastric cancer and metastatic lesions in the peritoneum, abdominal LNs, and bone. Furthermore, [68Ga]Ga-DOTA-FAPI-04 PET/CT provided more information for patients with recurrent disease and had the potential in monitoring response to treatment.

Characterization of the benign lesions with increased 68Ga-FAPI-04 uptake in PET/CT.

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).

68Ga-DOTATATE and 68Ga-NODAGA-JR11 PET/CT Images in a Patient With Gastric Neuroendocrine Tumor.

ABSTRACT: A 52-year-old man with newly diagnosed gastric neuroendocrine tumor (NET) underwent 68Ga-NODAGA-JR11 and 68Ga-DOTATATE imaging. 68Ga-DOTATATE PET/CT showed no 68Ga-DOTATATE uptake in the lesion, where 68Ga-NODAGA-JR11 showed intense uptake. The patient subsequently received endoscopic submucosal dissection and en bloc resection of the lesion, which was pathologically confirmed as gastric NET (G2). The positive findings of 68Ga-NODAGA-JR11 in the current case highlighted that 68Ga-NODAGA-JR11 PET/CT may be a promising molecular imaging technique for the detection of NETs with high sensitivity.

17ß-Estradiol Promotes Apoptosis of HepG2 Cells Caused by Oxidative Stress by Increasing Foxo3a Phosphorylation.

Liver cancer is associated with high mortality, particularly in patients infected with the hepatitis B virus. Treatment methods remain very limited. Here, we explored the effects of 17ß-estradiol (E2) on apoptosis of various liver cell lines (LO2, HepG2, and HepG2.2.15 cells). Within a certain concentration range, 17ß-estradiol induced oxidative stress and apoptosis of HepG2 cells, downregulated ERα-36 expression, and increased Akt and Foxo3a phosphorylation. p-Foxo3a became localized around the nucleus but did not enter the organelle. The levels of mRNAs encoding manganese superoxide dismutase (MnSOD) and catalase, to the promoters of which Foxo3a binds to trigger gene expression, were significantly reduced in HepG2 cells. 17ß-estradiol had no obvious effects on LO2 or HepG2.2.15 cells. We speculate that 17ß-estradiol may induce oxidative stress in HepG2 cells by increasing Foxo3a phosphorylation, thus promoting apoptosis. This may serve as a new treatment for hepatocellular carcinoma.

Increased 68Ga-FAPI-04 Uptake in Schmorl Node in a Patient With Gastric Cancer.

ABSTRACT: A 78-year-old man with a newly diagnosed gastric adenocarcinoma underwent 18F-FDG and 68Ga-FAPI-04 PET/CT before treatment. Both 18F-FDG and 68Ga-FAPI-04 PET/CT demonstrated intense radioactivity in the gastric cancer. However, the benign Schmorl node in the inferior endplate of the T5 vertebrae showed increased uptake of 68Ga-FAPI-04, which was not FDG avid. Two months after radical gastrectomy of the gastric cancer (pT1aN0M0, IA), a follow-up CT showed that the Schmorl node in T5 vertebrae remained unchanged.

Primary Central Nervous System Lymphoma Revealed by 68Ga-FAPI and 18F-FDG PET/CT.

ABSTRACT: A 67-year-old woman presented with left limb weakness, facial paralysis, and unsteady gait for 1 month. Brain MRI detected a mass in the right frontal lobe with prominent peritumoral edema, suggesting a malignant brain tumor. In 18F-FDG PET/CT, the mass was very FDG avid, and 68Ga-FAPI PET/CT showed the mass had heterogeneously mild to moderate increased uptake of the tracer. Histopathological examination after surgical resection of the mass confirmed the diagnosis of diffuse large B-cell lymphoma. The current case indicated the existence of fibrosis in the lymphoma lesion to some extent.

68Ga-DOTA-DiPSMA PET/CT Imaging: Biodistribution, Dosimetry, and Preliminary Application in Prostate Cancer.

Purpose: This prospective trial aimed to evaluate the safety, dosimetry, and biodistribution of a novel theranostic probe 68Ga-DOTA-DiPSMA. Also, we have performed the first preliminary application with 68Ga-DOTA-DiPSMA in prostate cancer (PCa) patients. Methods: Five healthy volunteers and ten PCa patients were injected with an intravenous bolus of 68Ga-DOTA-DiPSMA. They received serial whole-body PET scans from the time of injection up to 60 min post-injection, with a second PET/CT scanning at 120 min post-injection. In PCa patients, low-dose CT scan and whole-body PET were performed with 2 min per bed position in 40 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake and tumor lesion uptake were measured. A lesion-by-lesion analysis was performed. Results: 68Ga-DOTA-DiPSMA administration was safe and well-tolerated. The kidneys received the highest absorbed dose (114.46 ± 29.28 µSv/MBq), followed by the urinary bladder wall (100.82 ± 46.22 µSv/MBq) in accordance with the expected Prostate-Specific Membrane Antigen (PSMA) renal excretion of the tracer. The mean effective dose was 19.46 ± 1.73 µSv/MBq. The SUVmax of 68Ga-DOTA-DiPSMA PET/CT for PCa lesions, bone metastases, and lymph node metastases was 4.41 ± 2.72, 2.95 ± 1.11, and 3.26 ± 1.20, respectively. Conclusion: Injection of 68Ga-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. 68Ga-DOTA-DiPSMA shows favorable kinetics and imaging characteristics in patients who warrant further head-to-head comparison to validate 68Ga-DOTA-DiPSMA as an alternative for gallium-68-labeled PSMA clinical PET. Low nonspecific uptake in normal organs of 68Ga-DOTA-DiPSMA indicates potential radioligand therapy (RLT) application when labeled with 177Lu, 90Y, or 225Ac.