Massive bleeding from a gastric artery pseudoaneurysm in hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A case report.

BACKGROUND: The combination of atezolizumab (ATZ) and bevacizumab (BVZ) was approved as first-line systemic therapy for advanced hepatocellular carcinoma (HCC) owing to its superior rates of response and patient survival. However, ATZ + BVZ is associated with increased risk of upper gastrointestinal (GI) bleeding, including arterial bleeding, which is rare and potentially fatal. We present a case of massive upper GI bleeding from a gastric pseudoaneurysm in a patient with advanced HCC who had been treated with ATZ + BVZ. CASE SUMMARY: A 67-year-old man presented with severe upper GI bleeding after atezolizumab (ATZ) + bevacizumab (BVZ) therapy for HCC. Endoscopy failed to detect the bleeding site. Digital subtraction angiography revealed a gastric artery pseudoaneurysm and contrast extravasation from the inferior splenic artery and a branch of the left gastric artery. Successful hemostasis was achieved with embolization. CONCLUSION: HCC patients who have been treated with ATZ + BVZ should be followed for 3 to 6 mo to monitor for development of massive GI bleeding. Diagnosis may require angiography. Embolization is an effective treatment.

Case Report: Complete response after tislelizumab treatment in a hepatocellular carcinoma patient with abdominal lymph node metastasis.

Background: Abdominal lymph node (ALN) metastasis is associated with a poor prognosis in patients with hepatocellular carcinoma (HCC) because of the limited number of effective therapeutic options available. Immunotherapy with immune checkpoint inhibitors, such as those targeting programmed death receptor-1 (PD-1), have produced encouraging results in patients with advanced HCC. Here, we report a complete response (CR) in a patient with advanced HCC and ALN metastasis after combination treatment with tislelizumab (a PD-1 inhibitor) and locoregional therapy. Case summary: A 58-year-old man with HCC experienced progressive disease with multiple ALN metastases after undergoing transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and laparoscopic resection. Because the patient did not wish to receive systemic therapy, including chemotherapy and targeting therapy, we prescribed tislelizumab (as a single immunotherapeutic agent) together with RFA. After four tislelizumab treatment cycles, the patient achieved a CR without tumor recurrence for up to 15 months. Conclusion: Tislelizumab monotherapy can be effectively used to treat advanced HCC with ALN metastasis. Moreover, the combination of locoregional therapy and tislelizumab is likely to further increase therapeutic efficacy.

Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold.

Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [18F]10 and [18F]15 ([18F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [18F]15 demonstrated a better performance. In conclusion, [18F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans.

Biodegradable 131 Iodine-Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment.

Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg-1 of microspheres as well as favorable stability in vitro. Then, 131 I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of 131 I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I-CCMs treatment. In conclusion, these biodegradable 131 I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.

Radiomics based on 18 F-FDG PET/CT could differentiate breast carcinoma from breast lymphoma using machine-learning approach: A preliminary study.

PURPOSE: Our study assessed the ability 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) radiomics to differentiate breast carcinoma from breast lymphoma using machine-learning approach. METHODS: Sixty-five breast nodules from 44 patients diagnosed as breast carcinoma or breast lymphoma were included. Standardized uptake value (SUV) and radiomic features from CT and PET images were extracted using local image features extraction software. Six discriminative models including PETa (based on clinical, SUV and radiomic features from PET images), PETb (SUV and radiomic features from PET images), PETc (radiomic features only from PET images), CTa (clinical and radiomic features from CT images), CTb (radiomic features only from CT images), and SUV model were generated using least absolute shrinkage and selection operator method and linear discriminant analysis. The areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were calculated to evaluate the discriminative ability of these models. RESULTS: PETa and CTa models showed the best ability to differentiation in training and validation group (AUCs of 0.867 and 0.806 for PETa model, AUCs of 0.891 and 0.759 for CTa model, respectively). CONCLUSION: Models based on clinical, SUV, and radiomic features of 18 F-FDG PET/CT images could accurately discriminate breast carcinoma from breast lymphoma.

Ability of 18F-FDG PET/CT Radiomic Features to Distinguish Breast Carcinoma from Breast Lymphoma.

Purpose. To investigate the value of SUV metrics and radiomic features based on the ability of 18F-FDG PET/CT in differentiating between breast lymphoma and breast carcinoma. Methods. A total of 67 breast nodules from 44 patients who underwent 18F-FDG PET/CT pretreatment were retrospectively analyzed. Radiomic parameters and SUV metrics were extracted using the LIFEx package on PET and CT images. All texture parameters were divided into six groups: histogram (HISTO), SHAPE, gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), neighborhood gray-level different matrix (NGLDM), and gray-level zone-length matrix (GLZLM). Receiver operating characteristics (ROC) curves were generated to evaluate the discriminative ability of each parameter, and the optimal parameter in each group was selected to generate a new predictive variable by using binary logistic regression. PET predictive variable, CT predictive variable, the combination of PET and CT predictive variables, and SUVmax were compared in terms of areas under the curve (AUCs), sensitivity, specificity, and accuracy. Results. Except for SUVmin (p=0.971), the averages of FDG uptake metrics of lymphoma were significantly higher than those of carcinoma (p ≤ 0.001), with the following median values: SUVmean, 4.75 versus 2.38 g/ml (P < 0.001); SUVstd, 2.04 versus 0.88 g/ml (P=0.001); SUVmax, 10.69 versus 4.76 g/ml (P=0.001); SUVpeak, 9.15 versus 2.78 g/ml (P < 0.001); TLG, 42.24 versus 9.90 (P < 0.001). In the ROC curves analysis based on radiomic features and SUVmax, the AUC for SUVmax was 0.747, for CT texture parameters was 0.729, for PET texture parameters was 0.751, and for the combination of CT and PET texture parameters was 0.771. Conclusion. The SUV metrics in 18FDG PET/CT images showed a potential ability in the differentiation between breast lymphoma and carcinoma. The combination of SUVmax and PET/CT texture analysis may be promising to provide an effectively discriminant modality for the differential diagnosis of breast lymphoma and carcinoma, even for the differentiation of subtypes of lymphoma.

Functional Parameters of 18F-FDG PET/CT in Patients with Primary Testicular Diffuse Large B-Cell Lymphoma.

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), a hybrid imaging technique that simultaneously provides functional and anatomical information, has been reported to be useful in lymphoma. The present study was to evaluate the functional parameters of 18F-FDG PET/CT in patients with testicular diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed medical records of 5095 patients with lymphoma who treated at West China Hospital between March 2003 and January 2017, and selected patients with 18F-FDG PET/CT findings and subsequently biopsy confirmed the invasion of testis with DLBCL. Maximum standardized uptake values (SUVmax), peak standardized uptake values (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the patients were measured. We evaluated the characteristics of 18F-FDG PET/CT in this population. Six patients ranged in age from 37 to 73 years (median age, 58 years) were included in the analysis. The mean SUVmax was 11.09 and varied between 7.20 and 19.75; mean SUVpeak was 9.56 and ranged between 6.79 and 14.39. In addition, mean MTV 42% was 18.4 and varied between 1.3 and 61.6; mean MTV 2.5 was 34.7 and varied significantly between 1.6 and 141.9. With regard to TLG, mean TLG 42% was 168.906 and ranged from 7.514 to 687.004, while mean TLG 2.5 was 253.972 and ranged from 8.400 to 1127.802. In conclusion, 18F-FDG PET/CT scan is a useful tool in patients with testicular DLBCL. SUV, MTV, and TLG may vary a lot in different patients. SUVmax of testicular DLBCL lesion is relatively higher than that of normal testis. Also, we provided a set of MTV and TLG data and firstly showed their significant correlation with overall survival, which indicated a potential prognostic value of MTV and TLG. However, studies with larger population are needed to confirm these findings.

Quantification of radioactivity by planar gamma-camera images, a promoted method of absorbed dose in the thyroid after iodine-131 treatment.

Iodine-131 (131I) is an essential and widely used radioisotope in thyroid diseases and animal experiments. Planar imaging has been considered the most popular method for 131I thyroid uptake radioactive activity quantification. The ROI defining section is essential and can affect the accuracy of quantitative results. However, a consistent method has not been proposed. In this study, a UC-ROI defining method based on ULWL setting and colour display grade was applied. Three steps were performed: image acquisition of five standard activity models and obtaining the exact value that the counts per radioactive activity contributes to the ROI; image acquisition of 20 rat thyroids and obtaining the counts of the ROI (thyroid); and calculating the rat thyroid radioactive activity and comparing these values with the true values. The accuracy of quantification activity of 131I in rat thyroid reached 2.62% ± 0.41%. The mean quantification within 5% could be achieved in 19 of 20 rat thyroids. No significant difference existed between calculated thyroid 131I activity and true values with a paired matched-test (t = -0.384, P = 0.706 > 0.05). The results indicated that with the UC-ROI defining method, more accurate thyroid uptake 131I radioactive activity quantification by SPECT planar imaging can be achieved in vivo rat study.

[Preparation of 131I Labeled Collagen-Chitosan Microspheres and It's Antitumor Effect on Human Liver Cancer].

OBJECTIVE: To prepare iodine-131(131I) labeled biodegradable microspheres with chitosan and collagen for treating liver cancer. METHODS: Collagen-chitosan microspheres (CCMSs) were prepared with type-Ⅰ collagen and chitosan using emulsification-chemical cross-linking method. The size of the CCMSs were determined by electron microscope. 131I-CCMSs were achieved using Chloramine-T. The labelling rate of 131I was recorded. The stability of 131I-CCMSs in vitro were evaluated in PBS or human blood serum through 192 h incubation. The HepG2 model was established in nude mice 28 d after subcutaneous injection of 106 HepG2 cells. The model mice were sacrificed 7 d after injection of 131I-CCMSs,blank microspheres,or PBS (five mice in each group) into the HepG2 tumor xenografts. Samples of various organs were collected to determine the distribution of 131I-CCMSs. The curative effect of 131I-CCMSs on liver cancer was assessed by staining with HE for histological analyses. RESULTS: CCMSs were synthesized with a smooth and spherical shape and an average diameter of (5.1±1.2) µm. A radiolabeling rate of 86.10% was achieved. 131I radio-loading remained stable: 92.00% in saline and 83.00% in human serum after 192 h incubation. 131I was mainly concentrated in the subcutaneous tumor tissues. Potent curative effects of 131I-CCMSs on subcutaneous tumor tissues were demonstrated. CONCLUSION: Biodegradable CCMSs were successfully prepared and radiolabeled. The 131I-CCMSs exhibited potential curative effects on liver cancer,with high stability in vitro and in vivo.

Quantitative proteomics of CSF reveals potential predicted biomarkers for extranodal NK-/T-cell lymphoma of nasal-type with ethmoidal sinus metastasis.

AIM: Extranodal natural killer cell/T-cell lymphoma of nasal-type (NKTCL) is an aggressive human lymphoma, but its predicted biomarkers after chemotherapy are less known. The aim of this study is to find some potential predicted biomarkers in cerebrospinal fluid (CSF) of NKTCL patients with ethmoidal sinus metastasis (NESM). MATERIALS AND METHODS: The CSF samples were obtained from NKTCL patients with NESM before and after chemotherapy from Cancer Center of West China Hospital. Comparative proteomic profiling using label-free method was performed to characterize the fold change of proteins in NESM patients. KEY FINDING: In this study, 102 proteins with <1% false discovery rate in CSF of NKTCL with NESM patients were quantified. Furthermore, significantly reduced IGFBP2, SERP1NC1, AMBP and GPX3, as well as dramatically increased CPE levels were observed in the CSF of NKTCL patients after cytarabine chemotherapy. SIGNIFICANCE: IGFBP2, SERP1NC1, AMBP, GPX3 and CPE together or alone have a potential to be predicted indicators of NKTCL with NESM in response to chemotherapy.

Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis.

Background Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation. Purpose To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer. Material and Methods Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses. Results Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41-0.50) and 0.65 (95% CI, 0.56-0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions. Conclusion Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.

[Establishment of Bone Metastasis Model of Prostate Cancer in Mice with Monitoring of 18F-NaF PET-CT].

OBJECTIVES: To establish a mouse model bearing human prostate cancer xenograft with bone metastasis by the monitoring with X-Ray, Micro CT, and ¹8F-NaF PET/CT. METHODS: Sixteen male Balb/c nude mice were allocated into control (6 mice) and experimental group (10 mice). In experimental group, the mice were subjected to percutaneous injection of 2×105PC-3 cells into tibial plateau, bone defects were assessed after 21 d by X-ray, Micro-CT and ¹8F-NaF PET/CT, and bone damages were evaluated by HE staining. In control group, equal volume of saline was injected into the mice. RESULTS: At 21 d post modeling, the significant radioactive ¹8F--NaF signals were found in the tibial intramedullary cavity of all 10 mice in experimental group. The ROI value evaluation showed that SUVmaxin control group was 0.62±0.14, but SUVmaxin tumor group was 2.10±0.13, which indicated abnormal bone metabolism. The serum alkaline phosphate level and HE staining results also confirmed that tumor mediated bone destruction and osteogenesis. However, X-ray and Micro-CT did not indicate precise diagnostic bone defect. CONCLUSION: Bone metastasis model of prostate PC-3 cancer cells were successfully established by intratibial injection. ¹8F-NaF PET/CT could detect tumor invasion and bone osteogenesis in the early stage of modeling.

[Cellular Uptake and Localization of Novel NSCLC Penetrating Peptide with Neuropilin-1 Binding Motif].

OBJECTIVE: To synthesize and study the specific binding affinity of tumor-penetrating peptide YCCS to non-small cell lung carcinoma (NSCLC) cells in vitro. METHODS: YCCS peptide was designed by fusing the neuropilin-1 (NRP-1) binding sequence and NSCLC binding peptide CS. YCCS peptide was synthesized and fluorescent labeled with N-terminal FITC. NRP-1 positive human NSCLC cell A549, NRP-1 positive human breast cancer cell MDA-MB-231, normal human bronchial epithelium HBE135-E6E7 and human liver cell HL-7702 were incubated respectively, then we observed the specific binding affinity of tumor-penetrating peptide YCCS to NSCLC cells. RESULTS: After treated with 5 µmol/L peptide, significant fluorescent signals of FITC-YCCS peptide were demonstrated only in NSCLC A549 cells but marginal captured signal in MDA-MB-231, normal human HBE135-E6E7 or HL-7702 cells, which revealed specific NSCLC cells binding affinity. In 20 µmol/L treated group, non-specific binding were found in MDA-MB-231 and HL-7702 cells. CONCLUSION: The results of this novel designed YCCS peptide indicated a promising strategy for improving tumor penetrating with delivery capability of drugs to NSCLC A549 cells when treated with 5 µmol/L peptide.