Properties of [18F]FAPI monitoring of acute radiation pneumonia versus [18F]FDG in mouse models.

OBJECTIVE: In this study, the uptake characteristics of [18F]fibroblast activation protein inhibitor (FAPI) molecular imaging probe were investigated in acute radiation pneumonia and lung cancer xenografted mice before and after radiation to assess the future applicability of [18F]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response. METHODS: Initially, the biodistribution of [18F]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [18F]FAPI and [18F]fluorodeoxyglucose (FDG) PET/CT imaging efficacy in normal ICR, LLC tumor-bearing mice was evaluated. A radiation pneumonia model was then investigated using a gamma counter, small animal PET/CT, and autoradiography. The uptake properties of [18F]FAPI in lung cancer and acute radiation pneumonia were investigated using autoradiography and PET/CT imaging in mice. RESULTS: The tumor area was visible in [18F]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [18F]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [18F]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-ɑ decreased after thorax irradiation. Correspondingly, there was no notable [18F]FAPI uptake after irradiation, but there was an increase of [18F]FDG uptake in malignancies and lungs. CONCLUSIONS: The background uptake of [18F]FAPI is negligible. Moreover, the uptake of [18F]FAPI may not be affected by acute radiation pneumonitis compared to [18F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.

68Ga-FAPI PET imaging monitors response to combined TGF-ßR inhibition and immunotherapy in metastatic colorectal cancer.

BACKGROUNDImproving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor-ß receptor (TGF-ßR) inhibitor that targets cancer-associated fibroblasts (CAFs) is promising for the enhancement of efficacy of immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy.METHODSWe measured CAFs in vivo using the 68Ga-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) for PET/CT imaging to guide the combination of TGF-ß inhibition and immunotherapy. One hundred thirty-one patients with metastatic colorectal cancer (CRC) underwent 68Ga-FAPI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging. The relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed in patients. Mouse cohorts of metastatic CRC were treated with the TGF-ßR inhibitor combined with KN046, which blocks programmed death ligand 1 (PD-L1) and CTLA-4, followed by 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses.RESULTSPatients with metastatic CRC demonstrated high uptake rates of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. The TGF-ßR inhibitor enhanced tumor-infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamic changes of CAFs and tumor response to combined the TGF-ßR inhibitor with immunotherapy.CONCLUSION68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and the response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide precise TGF-ß inhibition plus immunotherapy in CRC patients, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.TRIAL REGISTRATIONCFFSTS Trial, ChiCTR2100053984, Chinese Clinical Trial Registry.FUNDINGNational Natural Science Foundation of China (82072695, 32270767, 82272035, 81972260).

18F-FAPI PET/CT performs better in evaluating mediastinal and hilar lymph nodes in patients with lung cancer: comparison with 18F-FDG PET/CT.

BACKGROUND: The aim of this study was to evaluate the efficacy of fluorine 18 (18F) labeled fibroblast activation protein inhibitor (FAPI) in identifying mediastinal and hilar lymph node metastases and to develop a model to quantitatively and repeatedly identify lymph node status. METHODS: Twenty-seven patients with 137 lymph nodes were identified by two PET/CT images. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of lymph node status were analyzed, and the optimal cut-off value was identified by ROC analysis. RESULTS: The SUVmax of metastatic lymph nodes on 18F-FAPI was higher than that on 18F-FDG PET/CT (10.87 ± 7.29 vs 6.08 ± 5.37, p < 0.001). 18F-FAPI presented much greater lymph node detection sensitivity, specificity, accuracy, PPV and NPV than 18F-FDG PET/CT (84% vs. 71%; 92% vs. 67%; 90% vs. 69%, 84% vs. 52%, and 92% vs. 83%, respectively). Additionally, the diagnostic effectiveness of 18F-FAPI in small lymph nodes was greater than that of 18F-FDG PET/CT (specificity: 96% vs. 72%; accuracy: 93% vs. 73%; PPV: 77% vs. 33%, respectively). Notably, the optimal cut-off value for specificity and PPV of 18F-FAPI SUVmax was 5.3; the optimal cut-off value for sensitivity and NPV was 2.5. CONCLUSION: 18F-FAPI showed promising diagnostic efficacy in metastatic mediastinal and hilar lymph nodes from lung cancer patients, with a higher SUVmax, especially in small metastatic nodes, compared with 18F-FDG. In addition, this exploratory work recommended optimal SUVmax cutoff values to distinguish between nonmetastatic and metastatic lymph nodes, thereby advancing the development of image-guided radiation. Trial registration ClinicalTrials.gov identifier: ChiCTR2000036091.

Elevated 18 F-AIF-FAPI-04 Uptake in Hepatic Hemangioma.

ABSTRACT: A 67-year-old woman who was diagnosed with intrahepatic cholangiocellular carcinoma (CCC) by biopsy underwent 18 F-FDG and 18 F-AIF-FAPI-04 PET/CT for initial and treatment assessment. In addition to CCC, she had a history of hepatic hemangioma for 3 years. 18 F-FDG PET/CT images showed increased uptake in CCC, but no uptake in hemangiomas. However, images on 18 F-AIF-FAPI-04 PET/CT indicated negative 18 F-AIF-FAPI-04 uptake in CCC, but intense activity in hemangiomas. Our case illustrates that hepatic hemangioma demonstrated intense 18 F-AIF-FAPI-04 uptake, and final diagnosis should be made with caution.

Preoperative 18F-FDG PET/CT radiomics analysis for predicting HER2 expression and prognosis in gastric cancer.

Background: We aimed to establish and validate 2 machine learning models using 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomic features to predict human epidermal growth factor receptor 2 (HER2) expression and prognosis in gastric cancer (GC) patients. Methods: We retrospectively enrolled 90 patients diagnosed with GC, including their clinical information and the 18F-FDG PET/CT images. Patients were allocated to a training cohort of 72 patients and an independent validation cohort (IVC) of 18 patients. There were 2,100 radiomic features extracted from the 18F-FDG PET/CT scans. A sequential combination of multivariate and univariate feature selection was applied, including sequential forward selection and a redundancy-based analysis. The justification of the model performance was conducted by cross-validation analysis on the training set and an independent validation analysis. Results: The machine learning models were developed using a balanced bagging approach for HER2 expression prediction and prognosis prediction, which differentiated HER2 positive expression from negative expression in the IVC with an area under the receiver operating characteristic curve (AUC) of 0.72, sensitivity of 0.85, and specificity of 0.80. The IVC for prognosis prediction achieved an AUC of 0.75, sensitivity of 0.82, and specificity of 0.71. We also conducted a reasonable interpretation for the selected features in each classification task from multiple aspects, including normalized feature importance analysis and statistical correlation analysis with the clinical features that were defaulted to be effective. Conclusions: 18F-FDG PET/CT radiomics analysis with a machine learning model provides a quantitative, efficient, and objective mechanism for predicting HER2 expression and prognosis in GC patients.

Application of a Novel 68Ga-HER2 Affibody PET/CT Imaging in Breast Cancer Patients.

Background: Breast cancer is a heterogeneous disease, and the human epidermal growth factor receptor 2 (HER2) expression may vary considerably between primary and metastatic lesions, or even within a single lesion. Repeated biopsies cannot always be performed. In this feasibility trial, we assessed whether a novel 68Ga-NOTA-MAL-MZHER2 (68Ga-HER2) affibody PET/CT could determine the HER2 status of each lesion if there was a clinical need for it. Methods: 68Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status remained unclear after standard examinations (including bone scan, 18F-FDG PET/CT, CT, and feasible biopsy). All available images for each patient were evaluated through an independent review of two committee-certified radiologists with nuclear medicine expertise. In case of discrepancy, adjudication by a third radiologist was performed as needed. All radiologists were blinded to the clinical information. Results: Twenty-four patients were enrolled. 68Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers, 13 with metastases not amenable to biopsy or repeated biopsy, 6 with inconsistent HER2 status between primary and metastatic lesions, and 4 with different HER2 status within different metastases. The final PET report revealed that the 68Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. The heterogeneity of 68Ga-HER2 affibody uptake was observed, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference between patients. 68Ga-HER2 affibody PET/CT demonstrated a high diagnostic accuracy in differentiating HER2-enriched breast cancer, with a sensitivity of 91.7% and a specificity of 84.6%, regardless of prior lines of anti-HER2 therapies. Conclusion: 68Ga-HER2 affibody PET/CT imaging could provide valuable information on HER2 expression of each tumor in the body of patients, which may help in personalized clinical decision-making. Its value is now under systemic assessment.

Is Performance of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography/Computed tomography (CT) or Contrast-enhanced CT Efficient Enough to Guide the Hilar Lymph Node Staging for Patients with Esophageal Squamous Cell Carcinoma?

Introduction: We evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT in the detection of hilar lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) to determine their value in guiding hilar lymph node staging and delineating radiation target volume. Methods: Consecutive patients with ESCC who underwent both PET/CT and contrast-enhanced CT before radical lymphadenectomy and esophagectomy at our institution from September 2009 to November 2018 were enrolled. The sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of FDG-PET/CT and contrast-enhanced CT for diagnosing hilar LNM were calculated. Results: Of the 174 patients included, contrast-enhanced CT predicted nine positive cases, while PET/CT predicted one, and eight (4.6%) were identified as pathologically positive for their resected hilar lymph nodes. The SE, SP, PPV, and NPV of PET/CT and contrast-enhanced CT were 0.000, 0.994, 0.000, and 0.954; and 0.125, 0.952, 0.111, and 0.958, respectively. The specificity showed a significant difference (P=0.037). PET/CT is slightly more specific than contrast-enhanced CT. Conclusions: PET/CT and contrast-enhanced CT may be useful tools for predicting the negativity of hilar LN status, but they are not recommended for guiding the hilar lymph node staging and the delineating of hilar LNM in radiotherapy planning of ESCC patients based on their low PPV.

18F-FDG PET/CT Radiomics for Preoperative Prediction of Lymph Node Metastases and Nodal Staging in Gastric Cancer.

OBJECTIVES: The accurate assessment of lymph node metastases (LNMs) and the preoperative nodal (N) stage are critical for the precise treatment of patients with gastric cancer (GC). The diagnostic performance, however, of current imaging procedures used for this assessment is sub-optimal. Our aim was to investigate the value of preoperative 18F-FDG PET/CT radiomic features to predict LNMs and the N stage. METHODS: We retrospectively collected clinical and 18F-FDG PET/CT imaging data of 185 patients with GC who underwent total or partial radical gastrectomy. Patients were allocated to training and validation sets using the stratified method at a fixed ratio (8:2). There were 2,100 radiomic features extracted from the 18F-FDG PET/CT scans. After selecting radiomic features by the random forest, relevancy-based, and sequential forward selection methods, the BalancedBagging ensemble classifier was established for the preoperative prediction of LNMs, and the OneVsRest classifier for the N stage. The performance of the models was primarily evaluated by the AUC and accuracy, and validated by the independent validation methods. Analysis of the feature importance and the correlation were also conducted. We also compared the predictive performance of our radiomic models to that with the contrast-enhanced CT (CECT) and 18F-FDG PET/CT. RESULTS: There were 185 patients-127 men, 58 women, with the median age of 62, and an age range of 22-86 years. One CT feature and one PET feature were selected to predict LNMs and achieved the best performance (AUC: 82.2%, accuracy: 85.2%). This radiomic model also detected some LNMs that were missed in CECT (19.6%) and 18F-FDG PET/CT (35.7%). For predicting the N stage, four CT features and one PET feature were selected (AUC: 73.7%, accuracy: 62.3%). Of note, a proportion of patients in the validation set whose LNMs were incorrectly staged by CECT (57.4%) and 18F-FDG PET/CT (55%) were diagnosed correctly by our radiomic model. CONCLUSION: We developed and validated two machine learning models based on the preoperative 18F-FDG PET/CT images that have a predictive value for LNMs and the N stage in GC. These predictive models show a promise to offer a potentially useful adjunct to current staging approaches for patients with GC.

18F-FDG PET/CT metabolic parameters and HER2 expression in colorectal cancer.

The relationship between 18F-FDG uptake and HER2 expression in colorectal cancer has not been investigated yet. This study aimed to investigate the predictive efficiency of preoperative 18F-FDG PET/CT for HER2 expression and prognosis in colorectal cancer. We retrospectively analyzed 131 colorectal cancer patients who underwent 18F-FDG PET/CT scans in our center before surgery. HER2 positivity was defined as a score of 2+ or 3+, and HER2 negativity was defined as a score of 0 or 1+ in immunohistochemistry of HER2 expression. The relationships between 18F-FDG PET/CT metabolic parameters and HER2 expression and the prognosis of colorectal patients were systematically studied. From 131 colorectal cancer patients, there were 27 (20.6%) HER2-positive patients. SUVmax of the primary tumor (mean ± SD) in the HER2-positive and the HER2-negative group was 18.238±8.912 and 14.455±6.531, respectively. SUVmax in the HER2-positive group was higher than in the negative group (p=0.034). When the cutoff was based on 5 cm, tumor size demonstrated significant positive correlations with SUVmax (p=0.012) and HER2 expression (p=0.014). Multivariate analysis showed that both SUVmax and tumor size had a significant correlation with HER2 expression (p=0.049 vs. p=0.043, respectively). There was no statistical difference in PFS between the HER2-positive and the HER2-negative group (p=0.28). 18F-FDG metabolic parameters had a significant correlation with HER2 expression in colorectal cancer. SUVmax combined with primary tumor size were better for predicting the HER2 status of colorectal cancer. 18F-FDG metabolic parameters had a significant correlation with HER2 expression in colorectal cancer. SUVmax combined with primary tumor size were better for predicting the HER2 status of colorectal cancer.

'Virtual experience' as an intervention before a positron emission tomography/CT scan may ease patients' anxiety and improve image quality.

INTRODUCTION: The aim of our study was to investigate the effect of a 'virtual experience' on reducing people's anxiety levels and improving image quality. METHODS: This study included 200 people who underwent 18 F-FDG PET/CT scan for the first time. Healthy people (n = 100) and patients (n = 100) were randomly divided into a control group and an intervention group. In the intervention group, we used a 'virtual experience' as an intervention before the scan. We used the Spielberger State-Trait Anxiety Inventory (STAI) and satisfaction questionnaires for evaluation. Additionally, the image quality was analysed. RESULTS: In the control group, more patients presented anxiety than healthy people (26(52%) versus 15(30%)) (P = 0.041). However, when the 'virtual experience' was provided, the number of cases of anxiety in the patient group decreased to 19(38%). Furthermore, patients in the intervention group had lower STAI-related scores than those in the control group (STAI-S: 37.08 ± 9.42 versus 43.34 ± 10.49, P = 0.109; STAI-T: 36.24 ± 9.55 versus 40.72 ± 9.00, P = 0.019). With respect to image quality, people who had higher STAI-related scores were more likely to have unqualified images. CONCLUSION: A 'virtual experience' provided by an audio-visual installation can ease patients' anxiety and improve image quality.

The Predictive Value of Early Changes in 18 F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: The aim of this study was to investigate the predictive value of early changes in 18 F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)-positive metastatic breast cancer. MATERIALS AND METHODS: Patients underwent 18 F-FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1-SUVmax on scan 2)/ SUVmax on scan 1] * 100%. RESULTS: In total, 294 18 F-FES-positive lesions from 36 patients were identified. The 18 F-FES SUVmax varied widely among lesions (median 5.7; range 1.8-32.4) and patients (median 5.1; range 2.5-13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from -5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression-free survival (PFS) than those with ΔSUVmax <38.0% (28.0 months vs. 3.5 months, p = .003). Multivariate analysis demonstrated that ΔSUVmax ≥38.0% was an independent predictor of PFS benefit in patients receiving fulvestrant therapy. CONCLUSION: Changes in SUVmax measured by serial imaging of 18 F-FES PET/CT could be used early to predict PFS benefit in patients receiving fulvestrant therapy. IMPLICATIONS FOR PRACTICE: The aim of this study was to evaluate the role of 18 F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to fulvestrant 500 mg therapy in patients with hormone receptor-positive/human epidermal growth receptor 2-negative metastatic breast cancer. This study highlights the utility of FES PET/CT as a predictive factor to discriminate patients who might benefit from fulvestrant. Moreover, these findings showed that this molecular imaging technique might be a potential tool for physicians to make individualized treatment strategies.

Electric manipulation of magnetism in bilayer van der Waals magnets.

The ferromagnetism of the two dimensional (2D) Cr2Ge2Te6 atomic layers with the perpendicular magnetic anisotropy and the Curie temperature 30-50 K has recently been experimentally confirmed. By performing the density-functional theory calculations, we demonstrate that the magnetic properties of bilayer Cr2Ge2Te6 can be flexibly tailored, due to the effective band structure tuning by the external electric field. The electric field induces the semiconductor-metal transition and redistributes charge and spin between the two layers. Furthermore, the magnetic anisotropy energy of the bilayer Cr2Ge2Te6 can be obviously enhanced by the electric field, which is helpful to stabilize the long-range ferromagnetic order. Our study about the electric manipulation of magnetism based on the band structure engineering generally exists in 2D magnetic systems and will be of great significance in low-dimensional all-electric spintronics.

Predictive Value of [18F]ML-10 PET/CT in Early Response Evaluation of Combination Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma.

PURPOSE: Apoptosis may be an indication of success therapy, and precise detection of apoptosis can provide instructional suggestions in the therapy management of malignant tumors. PROCEDURES: We used CNE-1 cell lines for in vitro experiments, and colony formation assay, CCK-8 assay, cell apoptosis analysis, and western blotting were performed. For in vivo experiments, subcutaneous xenotransplanted tumor models of CNE-1 in nude mice were established. Then, small animal positron emission tomography/X-ray computed tomography (PET/CT) images were acquired by tail intravenous injection of 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) or 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) before and 24 h and 48 h after treatment. Moreover, expression of epidermal growth factor receptor (EGFR), Ki-67, Glut-1, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was examined by immunohistochemical examination. Tumor volumes of mice were recorded every 2 days. RESULTS: In the presence of Cetuximab, the number of colonies of CNE-1 cells decreased significantly after irradiation at 1 and 2 Gy. In addition, Cetuximab increased the radiation-induced cytotoxicity and apoptosis of CNE-1 cells. Mechanistic studies demonstrated that Cetuximab enhanced radiosensitivity by suppressing the EGFR/PI3-K/AKT pathway. In PET/CT imaging, the tumors showed clear uptake of [18F]ML-10 at 24 h and 48 h after combined treatment, and the value of tumor/muscle (T/M) and SUVmax (the max of standard uptake value) was significantly higher than those of the other three groups. The T/M of [18F]ML-10 uptake showed a positive correlation of 0.926 with the apoptosis index (P < 0.001). However, the uptake of [18F]FDG in tumors exhibited no trend among the four groups. The T/M of [18F]FDG revealed a positive correlation of 0.926 with Glut-1 intensity (P < 0.001). CONCLUSIONS: Our work revealed that Cetuximab could increase the radiosensitivity of CNE-1 cells both in vitro and in vivo. Apoptosis imaging with [18F]ML-10 PET/CT is a promising modality for application in the response prediction of nasopharyngeal carcinoma.

First-principles investigation of the interface magnetic anisotropy of Fe/SrTiO3.

Interface effects in magnetic nanostructures play a critical role in the magnetic properties. By using first-principles density functional theory calculations, we investigate the electronic and magnetic properties of Fe/SrTiO3 interfaces, in which both the nonpolar surface SrTiO3(0 0 1) and the polar surface SrTiO3(1 1 0) are considered. A particular emphasis is placed on the magnetic anisotropy energy (MAE). Comparing MAE of the Fe/SrTiO3 interfaces and the corresponding Fe monolayers, we find the Fe/SrTiO3(0 0 1) interface decreases MAE, while the Fe/SrTiO3(1 1 0) interface increases MAE. The interface orbital hybridization and orbital magnetic moments are analyzed in detail to understand the different interface magnetic anisotropy. Our investigation indicates that interface engineering can be an effective way to modulate the magnetic properties.

Electrically induced 2D half-metallic antiferromagnets and spin field effect transistors.

Engineering the electronic band structure of material systems enables the unprecedented exploration of new physical properties that are absent in natural or as-synthetic materials. Half metallicity, an intriguing physical property arising from the metallic nature of electrons with singular spin polarization and insulating for oppositely polarized electrons, holds a great potential for a 100% spin-polarized current for high-efficiency spintronics. Conventionally synthesized thin films hardly sustain half metallicity inherited from their 3D counterparts. A fundamental challenge, in systems of reduced dimensions, is the almost inevitable spin-mixed edge or surface states in proximity to the Fermi level. Here, we predict electric field-induced half metallicity in bilayer A-type antiferromagnetic van der Waals crystals (i.e., intralayer ferromagnetism and interlayer antiferromagnetism), by employing density functional theory calculations on vanadium diselenide. Electric fields lift energy levels of the constituent layers in opposite directions, leading to the gradual closure of the gap of singular spin-polarized states and the opening of the gap of the others. We show that a vertical electrical field is a generic and effective way to achieve half metallicity in A-type antiferromagnetic bilayers and realize the spin field effect transistor. The electric field-induced half metallicity represents an appealing route to realize 2D half metals and opens opportunities for nanoscale highly efficient antiferromagnetic spintronics for information processing and storage.

Preoperative omental metastasis-related maximum standardized fluorine-18-fluorodeoxyglucose uptake value can predict chemosensitivity and recurrence in advanced high-grade serous ovarian cancer patients.

OBJECTIVE: The aim of this study was to explore the clinical and prognostic implication of preoperative fluorine-18-fluorodeoxyglucose uptake value of omental metastasis-related in advanced high-grade serous ovarian cancer patients (HGSC). PATIENTS AND METHODS: We retrospectively investigated HGSC patients with omental metastasis (International Federation of Gynecology and Obstetrics stage IIIB-IV) who underwent PET/CT before primary surgery in our hospital between January 2010 and January 2016. All patients were confirmed omental metastasis by postoperative pathology. None of these patients received neoadjuvant chemotherapy. PET/CT parameters, including maximum standardized uptake value of primary ovary tumor (SUVp), omental metastasis (SUVo), and omental metastasis-to-primary tumor (SUVo/p) were measured. The relationships between PET/CT parameters and clinical characteristics were analyzed by t-test. Kaplan-Meier methods and log-rank tests were used to analyze progression-free survival (PFS) in univariate analysis. For multivariate analysis, COX regression analysis was used to assess the prognostic predictive value of PET/CT-derived variables. RESULTS: Totally 81 advanced HGSC patients with omental metastasis were enrolled in our study, and 49 (60.5%) patients experienced recurrence and disease progression. The median (range) follow-up time was 18.5 (7-72) months. Older patients showed higher level of SUVo/p (P=0.006). Chemosensitive patients had lower levels of SUVo (P=0.009) and SUVo/p (P<0.001) than those chemoresistant ones. In univariate analysis, patients with better PFS were associated with lower SUVo (P<0.001) and SUVo/p (P<0.001). Multivariate analysis found only SUVo/p was an independent factor for PFS (P=0.006). CONCLUSION: Preoperative SUVo/p measured by fluorine-18-fluorodeoxyglucose PET/CT appeared to be an independent predictive factor for recurrence in advanced HGSC patients. Chemosensitive patients had lower omentum-related SUV values than those chemoresistant ones.

Glutaryl Polyamidoamine Dendrimer for Overcoming Cisplatin-Resistance of Breast Cancer Cells.

OBJECTIVE: Cisplatin has limited clinical applications due to drug resistance. PAMAM dendrimer was chosen as a vehicle to counteract cisplatin-resistance and its mechanism was assessed. METHODS: Generation 5 Polyamidoamine dendrimer (G5) was modified by glutaric anhydride (GA) and then conjugated with cisplatin. The cisplatin release of G5-GA-cisplatin was evaluated at pH 5.5 and pH 7.4. The cytotoxicity of G5-GA-cisplatin and free cisplatin was compared in cisplatin-resistant breast cancer cell line MCF-7R. The intracellular platinum content of MCF-7R was determined using ICP-MS. The expression of Ctr1 and ATP7B of MCF-7R cells was also evaluated. RESULTS: An average of 75 amino groups present in the G5 PAMAM surface were converted into glutaric acid (G5-GA75) and platinum loading was 350±21 µg per 1 mg of G5-GA75. G5-Ac75-cisplatin complex exhibited controlled release of cisplatin at different pH over a period of 96 h. After 96 h incubation with G5-Ac75-cisplatin, cell viability was 27.47±2.53%, 12.18±0.65% and 11.62±0.84% using platinum concentration of 1 µg/ml, 3 µg/ml and 5 µg/ml, respectively. Meanwhile, 46.33±5.06% cells survived even in the high platinum concentration of 5 µg/ml after 96 h incubation with free cisplatin. G5-GA75 led to 3-6 times higher cisplatin accumulation than free cisplatin in MCF-7R cells, because MCF-7R cells exhibited lower Ctr1 expression and higher ATP7B expression than MCF-7 cells. CONCLUSION: The G5-GA75-cisplatin complex displayed greater anticancer activity than free cisplatin in the cisplatin-resistant breast cancer cell line MCF-7R. The low levels of Ctr1 and high levels of ATP7B in MCF-7R caused G5-GA75 to allow the accumulation of cisplatin, which in turn increased the cytotoxicity. Results indicated that glutaryl G5 PAMAM may be a potential carrier for cisplatin targeting in breast cancer.

Development of tungsten bronze nanorods for redox-enhanced photoacoustic imaging-guided photothermal therapy of tumors.

Although various kinds of nanomaterials have been used as anticancer theranostics by exploiting the tumor microenvironment, relatively few nanomaterials can be efficiently activated by the tumor redox status for imaging and therapy. Oxygen-deficient tungsten-based oxides or bronzes are appearing as new classes of near-infrared (NIR)-responsive nanomaterials due to their unique properties such as tunable and broad NIR absorption. Herein, we synthesized PEG-Na x WO3 nanorods (NRs) by a simple thermal decomposition method and investigated their redox-activated performance for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT) of cancers. Both in vitro and in vivo studies revealed that such a novel class of tungsten bronzes with low toxicity could be used as efficient photothermal agents for PA imaging-guided PTT of cancers.

Chelator-Free Conjugation of 99mTc and Gd3+ to PEGylated Nanographene Oxide for Dual-Modality SPECT/MR Imaging of Lymph Nodes.

PEGylated ultrasmall nanographene oxide (usNGO-PEG) has exhibited a great potential in nanotheranostics due to its newly discovered physicochemical properties derived from the rich functional groups and bonds. Herein, we developed a general, simple, and kitlike preparation approach for 99mTc- and Gd-anchored NGO-PEG using a chelator-free strategy. In this strategy, [99mTcI(CO)3(OH2)3]+ (abbreviated to 99mTcI) and GdCl3 were mixed with usNGO-PEG to yield 99mTc- and Gd-usNGO-PEG via the synergistic coordination of N and O atoms from NGO and PEG with 99mTcI and Gd3+ without additional exogenous chelators. Under optimized conditions, the nanoprobes 99mTc- and Gd-usNGO-PEG were reliably prepared with high yields and good stability. Serial comparative experiments of the labeling yield, the measurements of -NH2 density and ζ-potentials, and various characterizations including energy-dispersive X-ray analysis spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy demonstrated that both usNGO and PEG synergistically provide the electron-donating atoms O and N to coordinate with 99mTcI and Gd to form stable nanocomplexes. Furthermore, both 99mTc- and Gd-usNGO-PEG exhibited excellent in vivo imaging of lymph nodes using single-photon emission computed tomography/computed tomography (SPECT/CT) and magnetic resonance (MR) imaging after local injection. Therefore, these results showed the successful establishment of 99mTc- and Gd-anchored usNGO-PEG using a chelator-free strategy and the potential of multimodality SPECT/CT and MR imaging of lymph nodes.