To develop a novel molecular scaffold designed for dual targeting via site-specific [99mTc] Tc labeling, we report its radiochemical evaluation and preliminary targeting efficacy in acidic tumor models. The pHLIP-RGD scaffold was synthesized by conjugating pHLIP variant 7 (var7) with cyclo(RGDfK) peptide. Pharmacokinetic assessment of [99mTc] Tc-pHLIP-RGD was performed in MDA-MB-231 xenograft-bearing mice through quantitative biodistribution studies and small-animal single photon emission computed tomography (SPECT) imaging. [99mTc] Tc-pHLIP-RGD demonstrated high stability in mouse serum for at least 4 h and exhibited strong binding affinity and specificity both in vitro and in vivo. Biodistribution studies revealed rapid tumor accumulation and prolonged retention, with uptake values of 7.01 ± 1.28, 4.23 ± 0.44, 8.04 ± 0.63, and 9.60 ± 1.26
Objectives: To prepare a novel 68Ga-labeled pH (low) insertion peptide-like peptide, YJL-11, and study its ability to be used as a probe for the diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. Methods: Circular dichroism (CD) analysis of YJL-11 was performed to assess its secondary structure. YJL-11 was labeled with 68Ga, and the in vivo biodistribution of 68Ga-YJL-11 in MDA-MB-231 xenograft mice was evaluated. This probe was then applied for small animal positron emission tomography (PET) imaging of tumor-bearing nude mice. Results: CD analysis of YJL-11 confirmed a typical pH-dependent transition in its secondary structure. The radiochemical yield of 68Ga-YJL-11 was 75.5 ± 0.25%, and the radiochemical purity was 95.75 ± 0.15%. Biodistribution studies showed that the tumor uptake of 68Ga-YJL-11 was significantly higher than in the control group, 1 and 2 h after injection. Small animal PET imaging results were consistent with the biodistribution data, showing clear images of the tumors and livers 1 and 2 h after injection of 68Ga-YJL-11, whereas tumors were not detected in the control group. Conclusion: 68Ga-YJL-11 was prepared with high radiochemical yield and can target TNBC tissues, indicating that it has great potential in the diagnosis of TNBC.
Abstract Background The aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N′,N″-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET). Results The radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P < 0.01). Of the measured off-target organs, 68Ga-YJL-4 was highly distributed in the liver and blood. The small animal PET imaging results were consistent with the biodistribution results. The tumors were visualized by PET at 2 and 4 h after the injection of 68Ga-YJL-4. No tumors were observed in the control group. Conclusions The novel pHLIP family peptide YJL-4 can adopt an α-helical structure for easy insertion into the cell membrane in an acidic environment. 68Ga-YJL-4 was produced in high radiochemical yield with good stability and can target TNBC tissue. Moreover, the strong concentration of radioactive 68Ga-YJL-4 in the abdomen does not hinder the imaging of early TNBC.
Objective To observe the effects of pHLIP[pH(low) insertion peptide]-P1AP on the proliferation of triplenegative breast cancer(TNBC) MDA-MB-231 cells. Methods Fluorescent-labeled pHLIP-P1AP was designed and synthesized. Protease-activated receptor 1(PAR1) expression on the surface of MDA-MB-231 cells and human MCF10A mammary epithelial cells were observed. The binding between fluorescent-labeled pHLIP-P1AP and MDA-MB-231 cells under different pH values(pH=7.4, 6.0) was analyzed. The effects of pHLIP-P1AP on the proliferation of MDA-MB-231 cells was analyzed under the conditions of pH 7.4 and 6.0. Results pHLIP-P1AP was successfully synthesized and fluorescentlabeled. PAR1 was highly expressed on the surface of MDA-MB-231 cells. In an acidic environment(pH 6.0), fluorescentlabeled pHLIP-P1AP and MDA-MB-231 cells had a high binding ability. In an acidic environment(pH 6.0), pHLIP-P1AP significantly inhibited the proliferation of MDA-MB-231 cells. With 0.5 μg, 1 μg, 2 μg, 4 μg, and 8 μg of pHLIP-P1AP,the cell proliferation inhibition rates were 3.39%, 5.27%, 14.29%, 22.14%, and 35.69%, respectively. Conclusion PAR1was highly expressed on the surface of MDA-MB-231 cells. pHLIP-P1AP can effectively target MDA-MB-231 cells in an acidic environment and inhibit the growth of MDA-MB-231 cells. Therefore, pHLIP-P1AP is expected to be a valuable new drug in the treatment of TNBC.
ObjectiveTo prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).MethodsThe pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).ResultsThe radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.Conclusion99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.
The pH (low) insertion peptide (pHLIP) family can target the tumor microenvironment (TME). If pHLIP can be labeled with radioiodine, the imaging and treatment of tumors can be considered. However, tyrosine and tryptophan can bind with iodine in the insertion region of pHLIP, and radioiodine labeling may affect the formation of α-helix structures in acidic environments; therefore, it is necessary to adjust the structure of pHLIP. This study aims to develop an 125I-labeled pH (low) insertion peptide variant 7-like peptide (pHLIP (Var7) LP) for imaging the TME in MDA-MB-231 triple-negative breast cancer (TNBC) xenograft tumor models. Based on pHLIP (Var7), a new peptide sequence, pHLIP (Var7) LP, was obtained by the sequence modification method and then characterized. The binding of pHLIP (Var7) LP to MDA-MB-231 cells was analyzed. pHLIP (Var7) LP was labeled with 125I by the iodogen iodination method. Serial biodistribution studies and small-animal single photon emission computed tomography (SPECT)/computed tomography (CT) imaging in subcutaneous MDA-MB-231 TNBC-bearing mice were performed using [125I] I-pHLIP (Var7) LP. A novel peptide, pHLIP (Var7) LP, has the characteristics of an α-helix structure, electronegativity, and amphiphilicity. Circular dichroism (CD) spectroscopy showed that the peptide presented a typical pH-dependent transition from an unstructured conformation to an α-helix structure when the pH was reduced from 8.0 to 4.0. The relative fluorescence intensities of 5-carboxytetramethylrhodamine (5-TAMRA)-pHLIP(var7) LP at pH = 6.0, 6.6, and 7.4 were 100.00 ± 5.98%, 72.10 ± 4.65%, and 13.72 ± 1.41%, respectively. The distribution of [125I] I-pHLIP (Var7) LP in tumors reached the highest level (8.7 ± 1.6% ID/g) at 2 h after injection, and the tumor-to-muscle ratios and tumor-to-blood ratios increased with time. Of the measured off-target organs, the stomach, kidney, and bladder showed higher uptake levels. SPECT imaging revealed rapid and sustained tumor uptake of [125I] I-pHLIP (Var7) LP in breast cancer-bearing mice. This study showed that [125I]I-pHLIP (Var7)LP had rapid and sustained tumor uptake in MDA-MB-231 TNBC and provided a new method for TNBC imaging and further treatment.
ABSTRACT:A 66-year-old woman having intermittent abdominal distention for 2 months was referred to our hospital. An enhanced abdominal CT scan showed multiple hepatic lesions, suspected of metastases. An 18F-FDG PET/CT scan, which was performed to seek primary tumor, showed multiple lesions with intense 18F-FDG uptake in the liver and lymph nodes located in cardiophrenic angle, abdominal cavity, and retroperitoneal space. All 18F-FDG-avid lesions were suspected of metastases. However, no suspected primary tumor was identified by the 18F-FDG PET/CT scan, which prompted the liver biopsy. Pathologic analysis revealed the presence of plasmacytoma.
The study describes an unusual case that a patient with previous history of adenocarcinoma of sigmoid colon who has developed chronic suppurative cholecystitis and peritonitis was misdiagnosed as metastasis. This case is presented to illustrate the importance of considering benign etiologies that may mimic metastatic disease when interpreting positron emmision tomography (PET)/CT scans.
The coronavirus disease 2019(COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) at the end of 2019 spread worldwide within only a few months. The screening and timely isolation of infected individuals have been regarded as an effective means of epidemic prevention and control. Therefore, effective screening of infected individuals plays a vital role in epidemic prevention and control. At present, reverse transcription-polymerase chain reaction(RT–PCR) is the main method for the in vitro detection of SARS-CoV-2. However, RT–PCR requires certified laboratories, expensive equipment, and trained technicians. Therefore, it is necessary to develop simpler and more convenient methods. Some studies have shown that the Pep KAA peptide has a high affinity for the S protein of SARS-CoV-2. The tyrosine in Pep KAA is labeled with 125 I and used to design a radioimmunoassay kit for the detection of the S protein of SARS-CoV-2, which is of great significance for the early diagnosis of COVID-19.
Objective:To evaluate the diagnostic efficacy of MDA-MB-231 triple-negative breast cancer with 125I-labeled pHLIP (Var7) by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging.Methods:The binding fraction of [125I]I-pHLIP (Var7) and MDA-MB-231 cells was measured at pH 7.4 and pH 6.0, and tumor-bearing mice were subjected to small-animal SPECT/CT imaging studies.Results:At pH = 6.0, the binding fractions of [125I]I-pHLIP (Var7) and MDA-MB-231 cells at 10 min, 40 min, 1 h, and 2 h were 1.9 ± 0.1%, 3.5 ± 0.1%, 6.3 ± 0.8%, and 6.6 ± 0.3%, respectively. At pH = 7.4, there was no measured binding between [125I]I-pHLIP (Var7) and MDA-MB-231 cells. Small-animal SPECT/CT imaging showed clearly visible tumors at 1 and 2 h after injection.Conclusions:[125I]I-pHLIP (Var7) could bind to MDA-MB-231 cells in an acidic environment, and small-animal SPECT/CT imaging showed clear tumors at 1 and 2 h after probe injection.
Objective:To establish and validate a malignant risk prediction model of solitary pulmonary nodules (SPNs) with pulmonary fibrosis in long-term smokers based on 18F-flurodeoxyglucose (FDG) PET/CT. Methods:PET/CT images of 222 SPNs combined with pulmonary fibrosis which were shown in integrated CT scan in 169 patients (all males; age 68(63, 75) years) were analyzed retrospectively. All patients were examined in PET/CT Center of the Affiliated Hospital of Qingdao University from January 2011 to December 2019 and all had definite smoking history. The benign and malignant nodules were judged according to the pathological diagnosis or follow-up imaging data of lung lesions (follow-up≥2 years). The clinical characteristics (age, smoking index), morphological characteristics (longest diameter of lesion, density, location, distribution, relative position of fibrosis, spiculation, lobulation, calcification, vacuole, vascular convergence, pleural indentation, emphysema and severity of bilateral pulmonary fibrosis) and metabolic characteristics (maximum standardized uptake value (SUV max)) of the benign and malignant lesions were analyzed by χ2 test and Mann-Whitney U test. Then multivariate logistic regression analysis was applied to select independent risk factors of malignant nodules, and a risk prediction model was established and verified by the area under the receiver operating characteristic (ROC) curve and k-fold cross validation ( k=10) respectively. Results:Among 169 patients, 222 SPNs were detected (157 malignant nodules, 65 benign nodules). Univariate analysis showed that smoking index, speculation, lobulation, vascular convergence sign, calcification, emphysema, nodule size, relative position of nodule and fibrosis, SUV max and severity of bilateral pulmonary fibrosis were significantly different between the benign and malignant nodules ( z values: 2.514-9.858, χ2 values: 4.353-18.442, all P<0.05). Result of multivariate logistic regression analysis showed that calcification, vascular convergence and SUV max were the independent risk factors of malignant nodules combined with pulmonary fibrosis (odds ratio ( OR): 0.048-2.534, all P<0.05). The risk prediction model was as follow: P=1/(1+ e - x), x=-1.839-3.033×calcification+ 0.930×vascular convergence+ 0.754×SUV max(with calcification/vascular convergence=1, without calcification/vascular convergence=0). The area under ROC curve was 0.932(95% CI: 0.895-0.969), and the sensitivity and specificity of the model were 87.9% and 86.2%, respectively. Results of k-fold cross validation showed that the prediction accuracy of 10 test sets was 0.847±0.075, and was 0.862±0.010 in training sets. Conclusions:Calcification, vascular convergence and SUV max are independent risk factors of malignant SPNs combined with pulmonary fibrosis in long-term asymptomatic smokers. The model based on the above variables presents high diagnostic efficiency in diagnosing malignant SPNs.
Background: Based on the principle of oxime formation, F labeling of polypeptides can be achieved via a reaction between an aldehyde groupcontaining F-prosthetic group and an aminooxy-modified polypeptide. The focus of this study was to investigate the one-step synthesis of 2-[F] fluoro-2 -deoxyglucose (F-FDG)arginine-arginine-leucine (RRL) from open-ring FFDG and the aminooxy-modified RRL peptide cyclo(RRLfK)-ONH2 and to study the biological distribution of F-FDG-RRL in a nude mouse model of human neuroglioma. Materials and Methods: The aminooxy-modified RRL peptide cyclo(RRLfK)-ONH2 was used as the precursor to react with F-FDG at 100 °C and different pH values for 30 minutes to synthesize F-FDG-RRL. The labeling yield, radiochemical purity, and in-vitro stability of the product were measured, and the biological distribution of F-FDG-RRL in tumor-bearing nude mice was analyzed at 30 minutes, 60 minutes and 120 minutes. Results: The labeling yield of F-FDG-RRL was (25.5±5.0) % at a pH of 2.0, and its radiochemical purity was greater than 95%. F-FDG-RRL was mainly excreted through the kidneys, with rapid blood clearance. One hour after injection, the uptake of F-FDG-RRL in tumors was (1.83±0.12) injected dose per gram of tissue (%ID/g), with a tumor/muscle ratio of 7.03±0.04, a tumor/blood ratio of 4.36±0.21 and a tumor/brain ratio of 7.53±1.37. Conclusion: The synthesis of F-FDG-RRL can be achieved through oximation. This method is straightforward and easy to promote. F-FDG-RRL has rapid blood clearance and high uptake by tumors.
To construct an FDG PET/CT metabolic parameter-based model to predict early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). A total of 62 patients with HCC after LT were enrolled with a follow-up period of 1 year. Basic clinical, pathology, and laboratory data, CT features (CPLC), and PET metabolic parameters (CPLCP) were collected for model construction. A CPLC nomogram without metabolic parameters and a CPLCP nomogram with metabolic parameters were established. The net reclassification index (NRI) and integrated discrimination improvement (IDI) of the two models were calculated. The constructed model was compared with Milan criteria and University of California San Francisco (UCSF) criteria. The time-dependent area under the receiver operating characteristic curve (time-AUC) was used to compare the efficiency of the models, and the bootstrap method was used to for verification. Harrell’s concordance index (C-index) was used to evaluate the performance of these models. Decision curve analysis (DCA) was used to evaluate the clinical practicability of each model. Thirty out of 62 patients experienced a recurrence during the 1-year follow-up. BCLC stage (P = 0.009), MVI (P = 0.032), AFP (P = 0.004), CTdmax (P = 0.033), and MTV (P = 0.039) were the independent predictors. The CPLC nomogram and the CPLCP nomogram were established. Compared with the CPLC nomogram, the NRI of the CPLCP nomogram increased by 38.98% (95% CI = −18.77–60.43%) and the IDI increased by 4.40% (95% CI = −1.00–16.62%). The AUC value of the CPLCP nomogram was higher than those of Milan criteria and UCSF criteria in the time-AUC curve. Moreover, the CPLCP nomogram had a higher C-index (0.774) than other models. Finally, the DCA curve showed that clinical practicability of the CPLCP nomogram outperformed the Milan criteria and UCSF criteria. The CPLCP nomogram combining basic clinical data, pathology data, laboratory data, CT features, and PET metabolic parameters showed good efficacy and high clinical practicability in predicting the early recurrence of HCC after LT.
Background To develop a model of malignant risk prediction of solitary pulmonary nodules (SPNs) using metabolic characteristics of lesions. Methods A total of 362 patients who underwent PET/CT imaging from January 2013 to July 2017 were analyzed. Differences in the clinical and imaging characteristics were analyzed between patients with benign SPNs and those with malignant SPNs. Risk factors were screened by multivariate nonconditional logistic regression analysis. The self‐verification of the model was performed by receiver operating characteristic (ROC) curve analysis, and out‐of‐group verification was performed by k‐fold cross‐validation. Results There were statistically significant differences in age, maximum standardized uptake value (SUV max ), size, lobulation, spiculation, pleural traction, vessel connection, calcification, presence of vacuoles, and emphysema between patients with benign nodules and those with malignant nodules (all P < 0.05). The risk factors for malignant nodules included age, SUV max , size, lobulation, calcification and vacuoles. The logistic regression model was as follows: P = l/(1 + e ‐ x ), x = − 5.583 + 0.039 × age + 0.477 × SUV max + 0.139 × size + 1.537 × lobulation – 1.532 × calcification + 1.113 × vacuole. The estimated area under the curve (AUC) for the model was 0.915 (95% CI: 0.883–0.947), the sensitivity was 89.7%, and the specificity was 78.9%. K‐fold cross‐validation showed that the training accuracy was 0.899 ± 0.011, and the predictive accuracy was 0.873 ± 0.053. Conclusions The risk factors for malignant nodules included age, SUV max , size, lobulation, calcification and vacuoles. After verification, the model has satisfactory accuracy, and it may assist clinics make appropriate treatment decisions.
Purpose Protease-activated receptor 1 (PAR1) is a signaling protein ubiquitously present on the surface of tumor cells, and its homologous protein fragment, PAR1-activating peptide (P1AP), can inhibit protein signal transduction of PAR1/G in tumor cells. pH (Low) insertion peptide (pHLIP) can target the acidic tumor microenvironment (TME) and can be used as an excellent carrier to deliver P1AP to tumor cells for therapeutic purposes. Methods PAR1 expression on the surface of MDA-MB-231 cells and human MCF10A mammary epithelial cells was observed. The binding between fluorescent-labeled pHLIP(Var7)-P1AP and MDA-MB-231 cells under different pH values was analyzed. The effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 cells was analyzed under the conditions of pH 7.4 and 6.0. Results PAR1 was highly expressed on the surface of MDA-MB-231 cells. In an acidic environment (pH 6.0 and 5.0), fluorescent-labeled pHLIP(Var7)-P1AP and MDA-MB-231 cells had a high binding ability, and the binding ability increased with the decrease in pH. In an acidic environment (pH 6.0), pHLIP(Var7)-P1AP significantly inhibited MDA-MB-231 cell proliferation. With 0.5 μg, 1 μg, 2 μg, 4 μg, and 8 μg of pHLIP(Var7)-P1AP, the cell proliferation inhibition rates were 3.39%, 5.27%, 14.29%, 22.14%, and 35.69%, respectively. Conclusion PAR1 was highly expressed on the surface of MDA-MB-231 cells. pHLIP(Var7)-P1AP can effectively target MDA-MB-231 cells in an acidic environment and inhibit the growth of MDA-MB-231 cells by inhibiting the signal transduction of PAR1/G protein.
Purpose Lymphovascular invasion (LVI) impairs surgical outcomes in lung adenocarcinoma (LAC) patients. Preoperative prediction of LVI is challenging by using traditional clinical and imaging parameters. The purpose of this study was to investigate the value of the radiomics nomogram integrating clinical factors, CT features, and maximum standardized uptake value (SUVmax) to predict LVI and outcome in LAC and to evaluate the additional value of the SUVmax to the PET/CT-based radiomics nomogram. Methods A total of 272 LAC patients (87 LVI-present LACs and 185 LVI-absent LACs) with PET/CT scans were retrospectively enrolled, and 160 patients with SUVmax ≥ 2.5 of them were used for PET radiomics analysis. Clinical data and CT features were analyzed to select independent LVI predictors. The performance of the independent LVI predictors and SUVmax was evaluated. Two-dimensional (2D) and three-dimensional (3D) CT radiomics signatures (RSs) and PET-RS were constructed with the least absolute shrinkage and selection operator algorithm and radiomics scores (Rad-scores) were calculated. The radiomics nomograms, incorporating Rad-score and independent clinical and CT factors, with SUVmax (RNWS) or without SUVmax (RNWOS) were built. The performance of the models was assessed with respect to calibration, discrimination, and clinical usefulness. All the clinical, PET/CT, pathologic, therapeutic, and radiomics parameters were assessed to identify independent predictors of progression-free survival (PFS). Results CT morphology was the independent LVI predictor. SUVmax provided better discrimination capability compared with CT morphology in the training set ( P < 0.001) and test set ( P = 0.042). A total of 1409 CT and PET radiomics features were extracted and reduced to 8, 8, and 10 features to build the 2D CT-RS, 3D CT-RS, and the PET-RS, respectively. There was no significant difference in AUC between the 2D-RS and 3D-RS ( P > 0.05), and 2D CT-RS showed a relatively higher AUC than 3D CT-RS. The CT-RS, the CT-RNWOS, and the CT-RNWS showed good discrimination in the training set (AUC [area under the curve], 0.799, 0.796, and 0.851, respectively) and the test set (AUC, 0.818, 0.822, and 0.838, respectively). There was significant difference in AUC between the CT-RNWS and CT-RNWOS ( P = 0.044) in the training set. Decision curve analysis (DCA) demonstrated the CT-RNWS outperformed the CT-RS and the CT-RNWOS in terms of clinical usefulness. Furthermore, DCA showed the PETCT-RNWS provided the highest net benefit compared with the PET-RNWS and CT-RNWS. PFS was significantly different between the pathologic and RNWS-predicted LVI-present and LVI-absent patients ( P < 0.001). Carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pathologic LVI, histologic subtype, and SUVmax were independent predictors of PFS in the 244 CT-RNWS-predicted cohort; and CA125, NSE, pathologic LVI, and SUVmax were the independent predictors of PFS in the 141 PETCT-RNWS-predicted cohort. Conclusions The radiomics nomogram, incorporating Rad-score, clinical and PET/CT parameters, shows favorable predictive efficacy for LVI status in LAC. Pathologic LVI and SUVmax are associated with LAC prognosis.
Kimura's disease is a clinically rare, chronic, benign lymphoproliferative disorder of unknown etiology. A 36-year-old man presented with painless axillary swelling, which was suspected as lymphoma. PET/CT was performed for staging. The images showed multiple foci of increased activity in bilateral axillary and right inguinal lymph nodes. Laboratory tests revealed an increased eosinophil ratio and eosinophil count. Pathological examination from dissected axillary lymph nodes was consistent with Kimura's disease.
Objective To analyze the expression of glucose transport protein (Glut)-l,Glut-3 and hexokinase (HK)-Ⅱ in non-small-cell lung cancer (NSCLC) lesions and pulmonary inflammatory lesions and discuss the correlation of them with 18F-fluorodeoxyglucose (FDG) uptake.Methods Twenty-four patients with NSCLC and 22 patients with pulmonary inflammatory lesions (25 males,21 females;age range:37-81 years) who underwent PET/CT from November 2012 to May 2016 were retrospectively analyzed.All patients had surgery and were confirmed by pathology.The expression of Glut-1,Glut-3 and HK-Ⅱ in the lesions was detected by immunohistochemistry.Immunohistochemical staining scores and maximum standardized uptake value (SUVmax) were calculated.One-way analysis of variance,the least significant difference t test,two-sample t test and Spearman correlation analysis were used.Results The SUVmax of NSCLC lesions was 8.71 ± 7.62,higher than that of pulmonary inflammatory lesions (3.29 ± 2.16;t =3.220,P< 0.05).Immunohistochemical staining scores of Glut-1,Glut-3 and HK-Ⅱ were 3.75±0.99,4.04±1.00 and 4.00±0.78 for NSCLC lesions respectively,and were all higher than those of pulmonary inflammatory lesions (2.32±0.65,2.89±0.83,2.41±0.50;t values:5.340,5.160,8.130,all P<0.01).The expression of Glut-1 and HK-Ⅱ was positively correlated with SUVmax in NSCLC lesions (rs values:0.414,0.457,both P<0.05).The expression of Glut-1,Glut-3 and HK-Ⅱ was not correlated with SUVmax(rs values:0.392,0.070,-0.066,all P>0.05),but the expression of Glut-3 was higher than that of Glut-1 and HK-Ⅱ (F=4.123,t values:0.970,0.150,all P<0.05) in pulmonary inflammatory lesions.Conclusions The expression of Glut-1,Glut-3 and HK-Ⅱ is higher in NSCLC lesions than that in pulmonary inflammatory lesions.Glut-1 and HK-Ⅱ are the important factors for 18F-FDG uptake in NSCLC.Glut-3 may play an important role in 18F-FDG uptake in pulmonary inflammatory lesions.
目的:探讨乳腺癌术前TNM分期对术后18F-FDG PET/CT阳性显像即转移的影响.方法:随访2012年—2016年间于我院P E T/C T中心进行检查的乳腺癌术后患者,并剔除假阳性与假阴性病例,最终纳入研究病例共计100例.以术后PET/CT显像结果为诊断标准,将全部患者分为转移组与未转移组,分析术前TNM分期对术后18F-FDG PET/CT阳性显像的影响.结果:100例患者中,转移患者71例,未转移患者29例.根据AJCC第7版乳腺癌TNM分期:原位癌(Tis期)及肿瘤大小为T1期的患者共54例,其中转移35例,未转移19例;T2期的患者共46例,转移36例,未转移10例;淋巴结转移状态N0期共28例,其中转移13例,未转移15例;N1期共27例,转移19例,未转移8例;N2期共26例,转移21例,未转移5例;N3期共19例,转移18例,未转移1例.单因素分析中,N分期是术后早期转移的影响因素(χ2=14.620,t=0.002<0.05);T1与T2期的术后转移率差别无统计学意义.二项l o g i s t i c s回归分析显示,术前淋巴结分期为N1、N2、N3期的患者术后发生转移概率大于分期为N0期的患者(O R=2.937,5.385,29.077,P=0.03,0.04,0.02<0.05).T分期在回归分析中P均大于0.05,没有统计学意义.结论:术前N分期越高术后发生转移的风险越高,应尽早干预.对直径5cm以下的肿瘤其肿瘤大小与术后转移无关,即肿瘤的增大不会增加转移的风险,可作为手术的适应症.
The present study aimed to observe the effect of the Notch1 signaling inhibitor γ-secretase inhibitor II (GSI II) on the growth and differentiation of tumor cells. The tumor cell line U87 was grown in serum-free media, and cell growth was evaluated using immunofluorescence. Single-cell wall-adherent growing conditions were prepared, GSI II was added, and the differentiation and growth of single tumor cells was evaluated. Immunofluorescence demonstrated positive results for the expression of Nestin and cluster of differentiation 133. The cell proliferation rate was reduced following the addition of GSI II (P<0.05). GSI II may significantly inhibit the proliferation and differentiation of U87 tumor stem cells.