Prediction of the activity of early ankylosing spondylitis using radiomics texture analysis on short tau inversion recovery (STIR).

OBJECTIVES: The study aimed to explore the value of texture analysis of radiomics based on the short tau inversion recovery (STIR) sequence to evaluate the activity of bone marrow oedema of sacroiliac joints in early AS. METHODS: 43 patients with early AS whose data were randomly divided into the training cohort (n=116) and verification cohort (n=56) according to the ratio of 7:3. The optimal feature subsets were obtained by Mann-Whitney U-test, the minimum-Redundancy Maximum-Relevancy (mRMR), and then least absolute shrinkage and selection operator (LASSO) using these texture feature parameters, which were used to construct the final prediction model and obtained the Radscore. The ROC curve was performed to evaluate the performance of the model. The Spearman correlation test was used to analyse the correlation of various indicators. RESULTS: In the training cohort, to differentiate early AS sacroiliac joint bone marrow oedema between the active and stable groups, the AUCs of the Radscore, SPARCC and ADC were 0.81, 0.91, 0.78, respectively. In the validation cohort, the AUCs were 0.87, 0.89, 0.85. In the two cohorts, there were no significant differences in AUCs between values of the Radscore and SPARCC, ADC (p>0.05). There was a significant difference in AUC between SPARCC and ADC in the training cohort (p<0.05), with no statistical significance in the validation cohort (p>0.05). The correlations were all low between the Radscore values and the values of ESR, CRP, tI, ASDAS-ESR and ASDAS-CRP (p<0.05). CONCLUSIONS: Radiomics analysis based on STIR texture analysis has a good prediction for the evaluation of bone marrow oedema activity of sacroiliac joints in AS. It can be a new non-invasive and objective evaluation method for AS activity.

Value of 18F-FDG PET/CT in patients with hepatic metastatic carcinoma of unknown primary.

PURPOSE: This retrospective study aimed to investigate the clinical value of -deoxy-2-(F)-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in detecting primary lesions of hepatic metastases. METHODS: A total of 124 patients with hepatic metastatic carcinoma of unknown primary underwent whole body F-FDG PET/CT imaging. According to the final diagnoses for both primary sites and hepatic metastases that were confirmed either histopathologically or by clinical follow up, all patients were divided into 4 groups: a true positive group (TP, 95 cases), a false positive group (FP, 9), a true negative group (TN, 8) and a false negative group (FN, 12). RESULTS: The TP rate of primary lesions, detected by F-FDG PET/CT, was 76.61%, the FP rate 7.26%, the TN rate 6.45% and the FN rate 9.68%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of F-FDG PET/CT in the detection of primary tumors were 88.78%, 52.94%, 91.35%, 40%, and 83.06%, respectively. Accurate diagnosis groups (TP, TN) showed a significantly higher SUVmax (standard uptake maximum value) level than that in error diagnosis groups (FP, FN). The SUVmax between hepatic metastases and primary lesions had a positive correlation. The primary tumor sites of hepatic metastases were mainly located in the gastrointestinal organs and the lungs. CONCLUSIONS: Whole body F-FDG PET/CT imaging was sensitive for detecting primary sites/lesions with hepatic metastatases of unknown primary, especially when the SUVmax of hepatic metastases were greater than 4.7.

Efficacy of neurointervention combined with intravenous thrombolysis in the treatment of ischemic cerebrovascular disease and its influence on neurological function and prognosis of patients.

The present study aimed to investigate the efficacy of neurointervention combined with intravenous thrombolysis in the treatment of ischemic cerebrovascular disease (ICD) and its influence on the neurological function and prognosis of patients. A total of 119 patients with ICD admitted to Xinxiang Central Hospital (Xinxiang, China) from May 2013 to September 2015 were selected. Among them, 65 patients were enrolled in the control group and treated with intravenous thrombolysis, whereas the other 54 patients were enrolled in the observation group and were treated with intravenous thrombolysis combined with neurointervention. The National Institute of Health Stroke Scale (NIHSS) system was used to evaluate the neurological function of patients after treatment. Kaplan-Meier survival curve analysis was carried out to assess the survival of patients. The total effective rate, complications, vascular recanalization and the hospitalization time after treatment were compared between the two groups. The NIHSS scores at 1, 3 and 6 months after treatment were statistically lower in the observation group than those in the control group (P<0.05). The total effective rate and total vascular recanalization in the observation group were higher than those of the control group (P<0.05). The incidence of complications in the observation group was statistically lower than that in the control group (P<0.05). In conclusion, neurointervention combined with intravenous thrombolysis can not only effectively improve the diseased blood vessels of patients and restore the damaged nerve function, but also reduce the incidence of complications. Moreover, neurointervention combined with intravenous thrombolysis is safe and can ensure a better quality of life of patients.

Withdrawn: The radiosynthesis of novel PI3K inhibitor, 8-ethoxy-2-(4-[18 F] fluorophenyl)-3-nitro-2H-chromene (18 F-EFPNC).

Withdrawal: Jianfeng Liu et al. 'The radiosynthesis of novel PI3K inhibitor, 8-ethoxy-2-(4-[18 F]fluorophenyl)-3-nitro-2H-chromene (18 F-EFPNC)', Journal of Labelled Compounds and Radiopharmaceuticals (https://doi.org/10.1002/jlcr.3524). The above article, published online on 30 May 2017 on Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal's Editor-in-Chief Committee, and John Wiley & Sons Ltd. The withdrawal has been agreed as it was not possible to complete corrections and finalise the article.

Clinical application of diffusion-weighted imaging and dynamic contrast-enhanced MRI in assessing the clinical curative effect of early ankylosing spondylitis.

The study aimed to demonstrate the clinical application value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing a clinical curative effect of early ankylosing spondylitis (AS).Forty-eight patients with early AS who were already treated combinations by traditional Chinese and Western medicine were involved in this study. All subjects underwent the conventional MRI, DWI, and DCE-MRI scanning of bilateral sacroiliac joints before and after treatment. The relevant data, such as the mean apparent diffusion coefficient (ADC) value, time-intensity curve of subarticular surface bone marrow, and the relationship between ADC value and enhancement factor (Fenh), enhancement slope (Senh), and time to peak (TTP), were obtained.1. The mean ADC value of the subarticular surface bone marrow of patients and after clinical treatment was (5.05 ±â€Š1.10) × 10 and (4.34 ±â€Š0.55) × 10 mm/s in ilium and (4.63 ±â€Š0.79) × 10 and (3.96 ±â€Š0.23) × 10 mm/s in sacrum, respectively. 2. In the DCE-MRI follow-up treatment imaging of 48 patients with AS (192 parts), the TIC curve type recorded was as follows: 43.75% (84/192) of type II, 56.25% (108/192) of type III, and type I curve was not seen. The number of type II curve was significantly reduced for pre treatment group (84 cases) compared with that post treatment group (124 cases). The Fenh, Senh, and TTP values were respective (113.38 ±â€Š44.71)%, (60.94 ±â€Š38.56)% min, (129.52 ±â€Š42.66) s in ilium and (83.03 ±â€Š20.39)%, (44.91 ±â€Š15.19)% min, (123.44 ±â€Š28.50) s in sacrum before clinical treatment. After the treatment, the Fenh, Senh, and TTP values were respective (75.90 ±â€Š17.97)%, (33.96 ±â€Š11.36)% min, (138.67 ±â€Š26.60) s in ilium and (73.28 ±â€Š15.67)%, (31.92 ±â€Š8.15)% min, (140.19 ±â€Š19.88) s in sacrum. The Fenh, Senh, and TTP values of semiquantitative indexes before and after clinical treatment were significantly different.DWI and DCE-MRI sequences can help evaluate the degree of active changes in AS inflammation and treatment effect in patients with early AS, and provide reliable imaging evidence.

The efficacy of 99mTc-MIBI imaging in 125I seed implantation treatment of rabbit VX2 transplanted liver cancer.

PURPOSE: To evaluate the efficacy of 99mTc-MIBI imaging in the evaluation of 125I radioactive particle implantation for treatment of rabbit VX2 transplanted liver cancer. METHODS: Twelve New Zealand white rabbit VX2 liver cancer models were successfully prepared by tumor cell suspension method and randomly divided into a control group and treatment group. The treatment group received 125I particle implantation according to the TPS plan, and the control group received the same number of hollow particle implantation. 99mTc-MIBI imaging was performed before and 7 d, 14 d, and 28 d after implantation. The target lesion (target, T) and normal liver tissue (nontarget, N) were determined by region of interest (ROI) technique. Radioactivity count was used to calculate the 99mTc-MIBI uptake ratio (target-to-nontarget ratio, T/N) between the target lesion and normal liver tissue, thereby obtaining early ratio (ER) and delayed ratio (DR), respectively. The retention index (RI) was calculated. The mice were sacrificed after 28 days for histopathologic observation. RESULTS: The T/N ratio, ER, and DR showed no statistical changes following the implantation time in the control group. In the treatment group, ER and DR gradually decreased after implantation of 125I seeds (P < 0.05). There was no significant difference in RI during different observation times between the treatment group and the control group. Compared with the treatment group, RI exhibited no statistical difference between before and 7 d, 7~14 d, and 14~28 d after implantation (P > 0.05). CONCLUSION: This method has value in evaluating the efficacy of 125I seed implantation treatment of rabbit VX2 transplanted liver cancer. The T/N ratio is independent of the tumor diameter, but is related to the blood perfusion and metabolic state of the tumor. Implantation of 125I particles into the rabbit transplanted liver cancer can effectively inhibit tumor growth, thus is a safe and effective method.

Autophagy is essential for flavopiridol­induced cytotoxicity against MCF­7 breast cancer cells.

Flavopiridol (FP) exerts antitumoral effects by triggering tumor cell cycle arrest and cytotoxicity in human breast cancer cell lines. The potent antitumor activity of FP is through its inhibition of cyclin­dependent kinases; however, this may not be the only mechanism of action. The present study aimed to investigate whether FP is able to induce autophagy and to examine the effects of autophagy on cell death in FP­treated MCF­7 human breast cancer cells. MCF­7 cells were treated with either FP alone or FP in combination with chloroquine (CQ). Expression levels of autophagy­related protein LC3B­II and p62/sequestosome 1 (SQSTM1) were used to monitor autophagic flux. MCF­7 cells were transfected with autophagy­related 5 (ATG5) small interfering (si)RNA to block autophagy. Cell viability and cell cycle status were determined. Following incubation with FP, MCF­7 cells exhibited significantly higher autophagy compared with untreated control cells, and the level of autophagy is comparable with cells under rapamycin induction, which was verified by immunodetection of LC3B­II and p62/SQSTM1 expression and inhibition by CQ. The addition of CQ treatment or ATG5­siRNA transfection against autophagy components attenuated the cytotoxic effects of FP treatment of MCF­7 cells. Furthermore, this autophagy inhibition did not impair the FP­induced cell cycle arrest. These results revealed that autophagy may be involved in FP­induced MCF­7 cell death and autophagy inhibition enhanced the tumor cell pro­survival ability. It is possibly that potential autophagy regulatory drugs may be used as a chemotherapy adjuvant.

Primary Left Tibial Epithelioid Hemangioendotheliomas With Multiple Metastases Revealed by FDG PET/CT Imaging.

Bone epithelioid angiosarcoma is an extremely rare osseous malignancy with an aggressive and destructive biological behavior. We present FDG PET/CT findings of a 59-year-old woman with left lower limb pain for 1 month. The images revealed abnormal activity in both left fibula and left tibia. In addition, abnormal activity in the sacrum and enlarged retroperitoneal lymph nodes was also noted. Pathological examination demonstrated bone epithelioid angiosarcoma.

Predictive Significance of a New Prognostic Score for Patients With Diffuse Large B-Cell Lymphoma in the Interim-Positron Emission Tomography Findings.

We hypothesized that the objective treatment response of patients with diffuse large B-cell lymphoma (DLBCL) was affected by many factors such as pathophysiological, biological, and pharmaceutical mechanisms. This retrospective study aimed to evaluate the predictive significance of clinical prognostic factors and interim fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), and to find a new prognostic predictor significantly associated with DLBCL patients' outcome. A total of 105 adult patients with DLBCL were reviewed. Each patient underwent an interim F-FDG PET/CT scan after the second chemotherapy cycle. The visual method based on the Deauville 5-point scale was used to evaluate the interim-PET/CT scans. The relationships among the prognostic factors, the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were analyzed with Kaplan-Meier plots. The predictive value of the newly constructed prognostic score was analyzed with multivariate analysis (Cox proportional hazard regression model). The visual analysis showed statistically significant differences in both PFS and OS between the patients with a negative interim-PET/CT and those with a positive interim-PET/CT. Advanced age, advanced stage, and DLBCL subtype were also significantly associated with outcome. A new prognostic score that composed of the above 4 factors was obtained. New prognostic score stratified patients into 4 risk groups with 3-year PFS of 98.5%, 73.9%, 11.1%, and 0%, and 3-year OS of 100%, 91.3%, 55.6%, and 0% (P < 0.001 for PFS and OS). Multivariate analysis showed that the new prognostic score had the greatest ability to predict relapse (P < 0.001) and death (P < 0.001). In DLBCL patients, interim F-FDG PET/CT can provide significant independent prognostic information. Our work illustrates that the new prognostic score has the strongest potential for accurately prognostication, for stratification in clinical trials, and for design of novel strategies for DLBCL patients in the high-risk group.

Overexpression of histone demethylase JMJD5 promotes metastasis and indicates a poor prognosis in breast cancer.

In this study, we showed the expression of JMJD5 was increased in breast cancer tissues and breast adenocarcinoma cell lines MCF-7 as well as triple negative breast cancer cell lines MDA-MB-231 compared with paired adjacent normal mammary tissues and normal mammary epithelial cell lines MCF-10A. The higher expression of JMJD5 was significantly corresponded with clinical stage, histological grade and lymph node metastasis. Overexpression of JMJD5 promoted cell invasion and induce EMT, while JMJD5 siRNA inhibits MDA-MB-231 cells invasion in vitro. Moreover, qChIP analysis revealed the Snail family proteins Snai1 was the direct target of JMJD5 in breast cancer cells. Luciferase reporter assays suggested that the overexpression of JMJD5 resulted in the activation of Snail1 promoter-driven luciferase reporter. The changes in the level of RNA and protein implied that the activation of Snail was the important mechanisms by which JMJD5 triggers metastasis. We also detected the higher expression of JMJD5 protein was an independent unfavorable biomarker for worse overall survival in breast cancer patients. Therefore, our results identified an important role for JMJD5 in breast cancer through the regulation of snail1.

Effect of 131I 'clear residual thyroid tissue' after surgery on the function of parathyroid gland in differentiated thyroid cancer.

Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) 'clear residual thyroid tissue' following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I 'clear residual thyroid tissue' treatment and underwent a whole body scan after 1 week to determine whether 'clear residual thyroid tissue' treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I 'clear residual thyroid tissue' treatment did not significantly impair the parathyroid function, thereby improving the treatment effect.

CT Perfusion Imaging Can Predict Patients' Survival and Early Response to Transarterial Chemo-Lipiodol Infusion for Liver Metastases from Colorectal Cancers.

OBJECTIVE: To prospectively evaluate the performance of computed tomography perfusion imaging (CTPI) in predicting the early response to transarterial chemo-lipiodol infusion (TACLI) and survival of patients with colorectal cancer liver metastases (CRLM). MATERIALS AND METHODS: Computed tomography perfusion imaging was performed before and 1 month after TACLI in 61 consecutive patients. Therapeutic response was evaluated on CT scans 1 month and 4 months after TACLI; the patients were classified as responders and non-responders based on 4-month CT scans after TACLI. The percentage change of CTPI parameters of target lesions were compared between responders and non-responders at 1 month after TACLI. The optimal parameter and cutoff value were determined. The patients were divided into 2 subgroups according to the cutoff value. The log-rank test was used to compare the survival rates of the 2 subgroups. RESULTS: Four-month images were obtained from 58 patients, of which 39.7% were responders and 60.3% were non-responders. The percentage change in hepatic arterial perfusion (HAP) 1 month after TACLI was the optimal predicting parameter (p = 0.003). The best cut-off value was -21.5% and patients who exhibited a ≥ 21.5% decrease in HAP had a significantly higher overall survival rate than those who exhibited a < 21.5% decrease (p < 0.001). CONCLUSION: Computed tomography perfusion imaging can predict the early response to TACLI and survival of patients with CRLM. The percentage change in HAP after TACLI with a cutoff value of -21.5% is the optimal predictor.

Imaging features of primary hepatic leiomyosarcoma: A case report and review of literature.

Primary hepatic leiomyosarcoma (PHL) is an extremely rare tumour. This tumour is difficult to diagnose by imaging examinations due to its rarity, and non-specific conventional imaging manifestations and clinical presentation. The present study reports the case of a 42-year-old male with PHL that was confirmed by histopathological and immunohistochemical examinations. Multimodal imaging examinations, including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT and digital subtraction angiography, were performed. The imaging manifestations were analysed and the associated literature was reviewed. The results found that no characteristic imaging appearance was present on ultrasound or plain CT scan. However, on unenhanced MRI, the tumours presented with a heterogeneous low signal density on T1-weighted imaging (WI) and a high signal density on T2WI and diffusion-WI. On gadopentetate dimeglumine enhanced MRI, the lesions were not enhanced during the arterial and portal venous phases; by contrast, these lesions were evidently enhanced during the 5-min delayed phase. Therefore, the delayed imaging of enhanced MRI is likely to be used to differentiate PHL from other hepatic tumours.

Imaging features of glucagonoma syndrome: A case report and review of the literature.

Glucagonoma syndrome appears as an extremely rare neuroendocrine tumour, with few studies ever having detailed its imaging manifestations. In particular, the magnetic resonance imaging (MRI) features of the lesion have not yet been reported. The present study describes a 54-year-old male who presented with uncontrollable skin erythema and weight loss that had been apparent for two years, and diabetes mellitus that had been apparent for five years. The glucagon level was 180 pg/ml. The plain abdominal computed tomography (CT) scan revealed a solid tumour in the neck of the pancreas, which was slightly reinforced during the arterial phase of the enhanced CT scan. Upon MRI, the lesion exhibited a low signal on T1-weighted imaging, and a slightly high signal on T2-weighted and half-Fourier acquisition single-shot turbo spin echo sequence imaging, which measured ~4.5×3.0×3.0 cm in size. Upon diffusion-weighted imaging, the lesion demonstrated heterogeneous hyperintensity, which was mildly enhanced during the arterial phase and washed out during the portal venous phase of gadopentetate dimeglumine-enhanced MRI. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET)-CT identified a mild uptake of 18F-FDG by the lesion. The patient was diagnosed with glucagonoma syndrome, and a distal pancreatectomy and splenectomy were subsequently performed. Microscopy revealed that the tumour cells exhibited nest- and belt-like arrangements. The immunohistochemical staining identified positive reactions for glucagon, synaptophysin and chromogranin A, which are consistent with a diagnosis of glucagonoma. Following surgery, the symptoms disappeared and the glucagon level returned to normal. In conclusion, imaging examinations are useful for determining the location and size of a glucagonoma. In particular, MRI is able to identify the distinctive morphological features of the lesion. Immunohistochemical staining provides diagnostic evidence based upon the neuroendocrine features.

MicroPET imaging of tumor angiogenesis and monitoring on antiangiogenic therapy with an (18)F labeled RGD-based probe in SKOV-3 xenograft-bearing mice.

So far, there is no satisfactory imaging modality to monitor antiangiogenesis therapy of ovarian cancer noninvasively. The aim of this study was to evaluate the effectiveness and sensibility of an (18)F labeled Arg-Gly-Asp (RGD) peptide in imaging and monitoring antiangiogenic responds in SKOV-3 xenograft-bearing mice. (18)F-FB-NH-PEG4-E[PEG4-c(RGDfK)]2 (denoted as (18)F-RGD2) was synthesized and employed in this study. Mice bearing ovarian cancer SKOV-3 tumors were used for biodistribution and microPET imaging studies compared with (18)F-FDG imaging. Animals were treated with low-dose paclitaxel and the effect of paclitaxel therapy on (18)F-RGD2 accumulation was investigated. Microvascular density (MVD) of SKOV-3 tumors was detected to assess the reliability of (18)F-RGD2 in antiangiogenesis monitoring. Biodistribution studies for (18)F-RGD2 revealed favorable in vivo pharmacokinetic properties, with significant levels of receptor-specific tumor uptake determined via blocking studies. MicroPET imaging results demonstrated high contrast visualization of SKOV-3 tumors. And tumor to background ratio (T/NT) of (18)F-RGD2 uptake was significantly higher than that of (18)F-FDG. Studies on antiangiogenic therapy demonstrated percentage of injected dose per gram of tissue (%ID/g) tumor uptake of (18)F-RGD2 which was obviously decreased in the treatment group than the control group, especially at 60 min (by 31.31 ± 7.18 %, P = 0.009) and 120 min (by 38.92 ± 8.31 %, P < 0.001) after injection of (18)F-RGD2. MVD measurement of SKOV-3 tumors confirmed the finding of the biodistribution studies in monitoring antiangiogenesis therapy. (18)F-RGD2, with favorable biodistribution properties and specific affinity, is a promising tracer for tumor imaging and monitoring antiangiogenesis therapy in ovarian cancer SKOV-3 xenograft-bearing mice.

Non-invasive imaging of allogeneic transplanted skin graft by 131I-anti-TLR5 mAb.

Although (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can be used for the non-invasive detection and monitoring of allograft rejection by activated leucocytes, this non-specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a (131)I-radiolabelled anti-Toll-like receptor 5 (TLR5) mAb for non-invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non-specific radiotracer (18)F-FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB/c mice transplanted with C57BL/6 skin grafts, with or without rapamycin treatment (named as allo-treated group or allo-rejection group), were injected with (131)I-anti-TLR5 mAb, (18)F-FDG, or mouse isotype (131)I-IgG, respectively. Whole-body phosphor-autoradiography and ex vivo biodistribution studies were obtained. Whole-body phosphor-autoradiography showed (131)I-anti-TLR5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The (131)I-anti-TLR5 mAb had significantly higher graft uptake and target-to-non-target ratio in the allo-treated group, as determined by semi-quantification of phosphor-autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high (18)F-FDG uptake was not observed in the allo-treated group. The highest allograft-skin-to-native-skin ratio (A:N) of (131)I-anti-TLR5 mAb uptake was significantly higher than the ratio for (18)F-FDG (7.68 versus 1.16, respectively). (131)I-anti-TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of (131)I-IgG was comparable in both groups. We conclude that radiolabelled anti-TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin.

Role of 18F-FDG PET/CT in detecting pelvic lymph-node metastases in patients with early-stage uterine cervical cancer: comparison with MRI findings.

OBJECTIVE: This study aimed to investigate the applied value of F-fluoro-2-dexoxyglucose (F-FDG) PET/computed tomography (CT) and MRI in detecting lymph-node metastasis in early-stage cervical cancer. MATERIALS AND METHODS: A retrospective study was performed on 87 early-stage cervical cancer patients evaluated with PET/CT and pelvic MRI before surgery. Histopathological evaluation of lymph nodes served as the diagnostic standard. F-FDG PET/CT and MRI images were analyzed and correlated with histopathological findings. RESULTS: The overall node-based sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 91% (61/67), 78.2% (61/78), 99.4% (1079/1085), and 98% (1140/1163), respectively, which were higher than the corresponding values of MRI, at 37.3% (25/67), 61% (25/41), 96.3% (1080/1122), and 95% (1105/1163) (P<0.034). The difference in diagnostic efficacy for identifying node-based metastases between PET/CT and MRI was significant (PET/CT vs. MRI, 0.719 vs. 0.587, P=0.017). Meanwhile, the overall patient-based sensitivity, PPV, NPV, and accuracy of PET/CT were 100% (34/34), 87.2% (34/39), 100% (48/48), and 94.3% (82/87), respectively, whereas the corresponding MRI values were 44% (15/34), 65% (15/23),74% (45/61), and 69% (60/87) (P<0.04). The difference in diagnostic efficacy for identifying patient-based metastases between PET/CT and MRI was significant (PET/CT vs. MRI, 0.974 vs. 0.705, P<0.001). CONCLUSION: PET/CT has been proven to be valuable in detecting lymph-node metastases. Compared with MRI, PET/CT has higher sensitivity, PPV, NPV, and accuracy in patients with early-stage cervical cancer for detecting lymphatic metastases.

Diversity of RGD radiotracers in monitoring antiangiogenesis of flavopiridol and paclitaxel in ovarian cancer xenograft-bearing mice.

INTRODUCTION: Although encouraging results had been shown in antiangiogenesis therapy monitoring, the underlying mechanism of RGD radiotracer accumulation needs to be further illustrated. This study was aimed to investigate the diversity of RGD radiotracers in monitoring antiangiogenic agent's effects and the underlying mechanism in ovarian cancer-bearing mice with a new agent flavopiridol compared with paclitaxel. METHODS: Ovarian cancer SKOV-3 xenograft-bearing mice were established and divided into three groups, flavopiridol, paclitaxel and control. Flavopiridol (5mg/kg body weight) and paclitaxel (20mg/kg body weight) were administered every 3 days for 16 days. Tumor growth and proliferation were monitored by caliper measurements and immunofluorescence staining. Antiangiogenic effects were determined by tumor microvessel density (MVD) in vivo and by endothelial cell tube formation assay in vitro, respectively. (99m)Tc-3P-RGD2 was prepared, and its biodistribution studies were carried out. The effect of antiangiogenesis therapy on integrin αvß3 expression was studied by immunohistochemical staining and flow cytometry. RESULTS: Both paclitaxel and flavopiridol therapy could apparently inhibit tumor growth and proliferation, and antiangiogenic effects of therapy were validated in vivo and in vitro. However, compared with the control group, ID%/g tumor uptake of (99m)Tc-3P-RGD2 showed a significant decrease at 2 hours (by 39.96%±8.23%, P=0.044) and at 4 hours (by 35.76%±11.42%, P=0.024) post injection in the paclitaxel-treated group, but a slight increase of tumor uptake in the flavopiridol-treated group at 2 hours (by 4.42%±0.24%, p=0.898) and at 4 hours (by 12.2%±1.84%, P=0.702). The further studies indicated flavopiridol therapy has a dual-effect, reducing integrin αvß3 expression on endothelial cells due to the reduction of tumor MVD and up-regulating the integrin αvß3 expression on tumor cells. CONCLUSIONS: There is diversity in evaluating antiangiogenic response when using (99m)Tc-3P-RGD2, which may be an important reminder in future clinical applications of RGD radiotracers as a strategy for antiangiogenesis therapy response monitoring.

Tumor vascular homing endgolin-targeted radioimmunotherapy in hepatocellular carcinoma.

Endoglin is a proliferation-associated cell membrane antigen and overexpressed in the angiogenic vasculature of solid tumors. However, the applications of endoglin (ENG)-targeted radioimmunotheray in hepatocellular carcinoma have not been reported yet. Therefore, the aim of this study was the visualization of both the development of hepatocellular carcinoma (HCC) tumor burden and therapeutic effect with ENG-targeted (131)I-anti-ENG mAb (A8), via in vivo noninvasive fluorescence imaging (NIFLI) of SMMC7721-green fluorescent protein (GFP) cells. A8 showed a dose-dependent, time-dependent suppression on the proliferation of SMMC7721-GFP cells and human umbilical vein endothelial cells (HUVECs) in vitro. Tube formation assay showed that (131)I-A8 markedly inhibits HUVECs to form extensive and enclosed tube networks. The results showed that the radiochemical purity of (131)I-A8 was 92.8 % and (131)I-A8 maintained more stable in serum than in saline and had high affinity against SMMC7721-GFP cells. The pharmacokinetics of (131)I-A8 was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. NIFLI exhibited a good relation between the fluorescent signal and tumor volume in vivo. Furthermore, treatment with (131)I-A8 resulted in significant tumor-growth suppression on the basis of the reducing fluorescent signal and a remarkably decreased tumor weight in treated animals. These results were further verified by RT-PCR and immunohistochemistry staining. Our findings indicate that (131)I-A8 can be used as ENG-targeted therapy for hepatocellular carcinoma, and noninvasive fluorescence imaging provides valuable information on tumor burden and effectiveness of therapy.

Non-invasive imaging of Toll-like receptor 5 expression using 131I-labeled mAb in the mice bearing H22 tumors.

Toll-like receptor 5 (TLR5) is overexpressed in several cancers and metastases, and presents an enticing target for molecular imaging of primary tumors. In the present study, 131I-anti-TLR5 monoclonal antibody (mAb) was evaluated for its use as a novel radiotracer for imaging hepatocarcinoma in mice bearing H22 tumors. The expression of TLR5 was analyzed by quantitative polymerase chain reaction and immunohistochemistry. The anti-TLR5 mAb and isotype immunoglobulin G (IgG) were radiolabeled with iodine-131 by the Iodogen method. The in vitro stability of iodinalized probes was determined in serum or saline for a series of times, and then evaluated with radio-thin-layer chromatography. The biodistribution study and autoradiography were performed in H22 tumor-bearing mice. It was found that H22-xenografted tumor tissue exhibited a higher level of TLR5 expression compared with normal liver tissues. 131I-anti-TLR5 mAb and 131I-IgG were obtained subsequent to purification, with high radiochemical purity (>95%), and remained stable for 48 h in human serum. The target-to-non-target ratio in the 131I-anti-TLR5 mAb group was significantly higher compared with the 131I-IgG group. The biodistribution study and autoradiography demonstrated that 131I-anti-TLR5 mAb was specifically retained in hepatocarcinoma with a high tumor uptake. Altogether, these results show that 131I-anti-TLR5 mAb is capable of detecting lesions in a TLR5-expressing tumor, with high target selectivity, and may offer a promising agent for hepatocarcinoma diagnosis and encourage further investigation.