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Purpose: Recurrence is the main cause of tumor-related death of retroperitoneal liposarcoma (RPLPS). Different recurrence pattern was determined by variant subtype of retroperitoneal liposarcoma which displayed diverse presentations on 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). This study aims to analyze the characteristics of different histologic subtypes of RPLPS on 18F-FDG PET/CT and their associations with recurrence and prognosis.Methods: Clinical-pathological information, 18F-FDG PET/CT, recurrence and progression free survivals (PFS) of 83 patients with RPLPS were collected. Maximum, and peak standardized uptake value (SUVmax and SUVpeak, respectively) and mean CT value (CTmean) of tumors were measured; their correlations with histologic subtype were analyzed. The predictability of SUVmax and CTmean for histologic subtype was evaluated using the receiver operating characteristics (ROC) curve analysis. ROC curve was also performed to analyze the predictive value of SUVmax and peak SUV (SUVpeak) for recurrence. The Kaplan-Meier analysis was performed to analyze whether SUVmax and SUVpeak were risk factors for recurrence. Results: Regarding the histology, 30.1% patients were well-differentiated liposarcoma (WDLPS), 56.6% patients were dedifferentiated liposarcoma (DDLPS), 12.0% patients were myxoid/round cell liposarcoma(MLPS), and 1.2% patients were pleomorphic liposarcoma (PMLPS). SUVmax of DDLPS were significantly higher than those of WDLPS (P < 0.001) and MLPS(P = 0.001). CTmean of WDLPS was significantly lower than those of MLPS (P = 0.001) and DDLPS (P < 0.001). ROC curve suggested 5.1 as an approximate cutoff value of SUVmax for distinguishing DDLPS from non-DDLPS (sensitivity = 76.8%, specificity = 88.0%), and 12.3Hu as cutoff value of CTmean for distinguishing WDLPS from non-WDLPS (sensitivitty = 94.1%, specificity = 54.5%). When the cut-off values of SUVmax and SUVpeak were set at 10.7 and 6.9 respectively, the maximum performances for predicting recurrence were obtained. Kaplan-Meier analyses showed that histologic subtype, SUVmax, and SUVpeak were risk factors that associated with recurrence-free survival (P = 0.02, ＜0.001, and 0.001, respectively).Conclusions: The SUV value and CT features on 18F-FDG PET/CT imaging may increase the confidence in diagnosis and subtype distinguish of RPLPS. When inflammatory liposarcoma was excluded, patients with SUVmax > 10.7 or SUVpeak > 6.9 suggest a poor prognosis.

Objective The aim of this study was to analyze the computed tomography (CT), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), and clinical findings of pulmonary epithelioid hemangioendothelioma. Methods Eighteen patients were included. We reviewed CT and PET/CT features and clinical information. Spearman correlation analysis was used to reveal the correlation between lesion size and maximum standardized uptake values (SUVmax). Results Eleven patients complained of different symptoms. The serum levels of tumor markers were elevated in 8 patients (44.4%). Multiple lesions were shown in 14 cases (77.8%). Eleven cases (61.1%) presented as bilateral multiple perivascular lesions. The size of the largest nodule was less than 20 mm in diameter in 11 cases (61.1%). Eleven cases underwent PET/CT examination, and 8 cases (72.7%) had increased FDG uptake. There was a positive correlation (Spearman correlation coefficient, 0.56; P = 0.009) between lesion size and SUVmax. Extrapulmonary involvement was shown in 7 cases, including the liver and bone. Conclusions Pulmonary epithelioid hemangioendothelioma on CT scan usually showed multiple bilateral perivascular lung nodules, generally measuring less than 20 mm in diameter. Lesions usually showed increased FDG uptake on PET/CT scans. There was a positive correlation between lesion size and SUVmax. The liver and bone were the most frequently involved extrapulmonary organs.

Background Previous reports suggested that CD133-positive cells had biological features of cancer stem cells (CSCs). Furthermore, CD133 expression was reported as an unfavorable prognostic factor in patients. Therefore, a new radiolabeled probe, 99mTc labeled AC133 antibody which binding with CD133 specifically, was developed to noninvasively detect CSCs by SPECT in vivo. Methods CD133 expression was evaluated by flow cytometry in three colon cancer cell lines (HCT116, Lovo and DLD1). AC133 antibody and control IgG were conjugated with succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH), and then labeled with 99mTc. The new radiolabeled probe was named as 99mTc-SHNH-AC133. The vitro cell binding assays, series SPECT imaging and biodistribution analyses were performed. Flow cytometry, immunofluorescence staining of tumor tissues were carried to verify the in-vivo imaging results. Results 99mTc-SHNH-AC133 was labeled with a high radiochemical purity (97.7±2.4%, N.=3) and specific activity (4.07 MBq/µg). Cellular experiments showed that the labeled AC133 antibody retained with a high binding affinity on CD133-positive cells (HCT116 and Lovo cells). Biodistribution analyses showed high tumor uptake of the tracer in HCT116 and Lovo xenografts (8.82±0.73 and 7.37±0.26 %ID/g, respectively, N.=4) and high tumor-to-muscle ratios (13.18±2.84 and 11.13±0.53, respectively, N.=4) at 36 h after injection, resulting in high contrast SPECT images with high specific tumor uptake. However, the tumor bearing CD133-negative cell (DLD1 cells) showed no obvious uptake of 99mTc-SHNH-AC133 both in-vitro cell binding and in-vivo imaging study. Moreover, the tumor uptake of 99mTc-SHNH-AC133 in positive tumor models was significantly reduced by pre-injection of excess unlabeled AC133 antibody. Flow cytometric analysis and immunofluorescence staining confirmed the CD133 expression in tumors, which correlated well with the in-vivo results. Conclusions This study showed that 99mTc-SHNH-AC133 exhibited high uptake in CD133-positive tumors. The high specificity and good tumor targeting properties of 99mTc-SHNH-AC133 may provide a new method to track or locate CSCs.

This study was designed to investigate the feasibility of imaging bone marrow stem cells (BMSCs) in experimental middle cerebral artery occlusion (MCAO) rat models with a reporter gene–probe system, HSV1-tk–131I-2′-fluoro-2′-deoxy-1-β-d-arabinofuranosyl-5-iodouracil (131I-FIAU), and to choose the best strategies for stem cell injection, image acquisition, and imaging in vivo. Methods: A recombinant adenovirus (Ad5-TIBE) carrying the herpes simplex virus type 1 thymidine kinase (TK) reporter gene (HSV1-tk) linked via the internal ribosome entry site to the brain-derived neurotrophic factor therapeutic gene was prepared. After transfection with Ad5-TIBE, BMSCs were introduced into MCAO rat models via local injection into the brain or via injection into the lateral ventricle, carotid artery, and tail vein. Normal rats were used as controls. Twenty-four hours after 131I-FIAU injection, rats were sacrificed for biodistribution analysis. The expression of the TK gene was evaluated by real-time quantitative polymerase chain reaction and Western blot analysis. Autoradiography was used for ex vivo imaging. SPECT images were obtained in MCAO rat models. Results: The percentage injected dose per gram (%ID/g) in infarcted brain tissue in rats receiving the injection into the brain was 0.124 ± 0.013; this value was significantly higher than those in rats receiving the injection into the ventricle (0.052 ± 0.004), carotid artery (0.061 ± 0.002), and tail vein (0.059 ± 0.005) as well as normal rats (0.005 ± 0.001). No differences were seen in the other cell transplantation groups. The %ID/g in infarcted brain tissue was higher than that in the contralateral brain tissue in all experimental rats but not in normal rats. The expression of the TK gene in rats receiving a local injection into the brain was superior to that in all of the other groups. TK messenger RNA and protein expression showed a positive correlation with the %ID/g in brain tissue. Greater radioactivity at the injection site than in the surrounding and contralateral brain tissues in all experimental rats was indicated through autoradiography. The ratio of counts in bilateral brain tissues reached its peak (6.63) 24 h after 131I-FIAU injection. SPECT images showed that radioactivity accumulation in the brain was low but increased gradually over time. Conclusion: The HSV1-tk–131I-FIAU reporter gene–probe system may be used to monitor BMSC activity in experimental MCAO rat models. Local injection of stem cells may provide an optimal means for cell transplantation, and imaging with 131I-FIAU 24 h after injection provides peak target-to-nontarget count ratios.

Introduction Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an 131 I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. Methods Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(−) cells by magnetic activated cell sorting. CD133(+), CD133(−), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n=5). AC133 mAb was labeled with 131 I by the iodogen method. Results The radiolabeled compound, 131 I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of 131 I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(−) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of 131 I-AC133 mAb was 6.97±1.40, 1.35±0.48, 6.12±1.91, and 1.61±0.44% ID/g (n=4) at day 7 after injection of 131 I-AC133 mAb in CD133(+), CD133(−), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of 131 I-AC133 mAb to CD133(+) tumors. Conclusions This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively.

Introduction EphA2, one member of the Eph receptor family, is widely expressed in multiple aggressive cancers. SWL, a small peptide identified by phage display, has high binding affinity to EphA2, suggesting that it could be exploited for targeted molecular imaging. Therefore, a novel peptide-based probe, 99m Tc-HYNIC-SWL, was developed and its potential to specifically target EphA2-positive tumors was investigated. Methods The SWL peptide was labeled with hydrazinonicotinic acid (HYNIC), followed by 99m Tc labeling. Immunofluorescence staining was carried out to detect the expression of EphA2 in A549 lung cancer cells and OCM-1 melanoma cells. Saturation binding experiments were performed by incubating A549 cells with increasing concentrations of radiolabeled peptide in vitro. To test the probe in vivo, nude mice bearing either A549 or OCM-1 derived tumors were established, injected with 99m Tc-HYNIC-SWL, and subjected to SPECT imaging. Mice injected with excess unlabeled SWL were used as a specific control. Ex vivo γ-counting of dissected tissues from the mice was also performed to evaluate biodistribution. Results Immunofluorescence staining showed that A549 cells intensively expressed EphA2, while OCM-1 cells had little expression. 99m Tc-HYNIC-SWL displayed high binding affinity with A549 cells (K D =2.6±0.7nM). From the SPECT images and the results of the biodistribution study, significantly higher uptake of the tracer was seen in A549 tumors (1.44±0.12 %ID/g) than in OCM-1 tumors (0.43±0.20 %ID/g) at 1h after injection. Pre-injection with excess unlabeled peptide in A549-bearing nude mice, significantly reduced tumor uptake of the radiolabeled probe (0.58±0.20 %ID/g) was seen. These data suggest that 99m Tc-HYNIC-SWL specifically targets EphA2 in tumors. Conclusions The expression of EphA2 can be noninvasively investigated using 99m Tc-HYNIC-SWL by SPECT imaging. The in vitro and in vivo characteristics of 99m Tc-HYNIC-SWL make it a promising probe for EphA2-positive tumor imaging.

The purpose of this study was to investigate and compare the feasibility of rat sodium iodide symporter ( rNIS ) and human sodium iodide symporter ( hNIS ) as reporter genes for noninvasive monitoring of rat bone marrow mesenchymal stem cells (rBMSCs) transplanted into infarcted rat myocardium. rBMSCs were isolated from rat bone marrow. Adenovirus (Ad) was reconstructed to contain rNIS-enhanced green fluorescent protein (eGFP) or hNIS-eGFP. The transfection efficiency of Ad/eGFP/rNIS and Ad/eGFP/hNIS to rBMSCs was measured by real-time polymerase chain reaction, flow cytometry, Western blot, and immunofluorescence staining. The transfected rBMSCs were transplanted into infarcted rat myocardium followed by a single-photon emission computed tomography (SPECT) study with 99m Tc-pertechnetate as the radiotracer and by autoradiography. The isolated rBMSCs were CD29, CD44, and CD90 positive and CD34, CD45, and CD11b negative. The expression of rNIS and hNIS in the transfected rBMSCs at both gene and protein levels was obviously higher than that without transfection. The myocardium of rats transplanted with transfected rBMSCs could be visualized by SPECT owing to the accumulation of 99m Tc-pertechnetate in rBMSCs mediated by exogenous NIS genes. The accumulation of 99m Tc-pertechnetate in myocardium mediated by rNIS was higher than that by hNIS , which was also confirmed by autoradiography. Both rNIS and hNIS are useful reporter genes to monitor BMSCs transplanted into infarcted myocardium in vivo with rNIS being superior to hNIS as the reporter gene.