Dengfeng Cheng

Morphological effect of oscillating magnetic nanoparticles in killing tumor cells

Forced oscillation of spherical and rod-shaped iron oxide magnetic nanoparticles (MNPs) via low-power and low-frequency alternating magnetic field (AMF) was firstly used to kill cancer cells in vitro. After being loaded by human cervical cancer cells line (HeLa) and then exposed to a 35-kHz AMF, MNPs mechanically damaged cell membranes and cytoplasm, decreasing the cell viability. It was found that the concentration and morphology of the MNPs significantly influenced the cell-killing efficiency of oscillating MNPs. In this preliminary study, when HeLa cells were pre-incubated with 100xa0μg/mL rod-shaped MNPs (rMNP, length of 200u2009±u200950xa0nm and diameter of 50 to 120xa0nm) for 20xa0h, MTT assay proved that the cell viability decreased by 30.9% after being exposed to AMF for 2xa0h, while the cell viability decreased by 11.7% if spherical MNPs (sMNP, diameter of 200u2009±u200950xa0nm) were used for investigation. Furthermore, the morphological effect of MNPs on cell viability was confirmed by trypan blue assay: 39.5% rMNP-loaded cells and 15.1% sMNP-loaded cells were stained after being exposed to AMF for 2xa0h. It was also interesting to find that killing tumor cells at either higher (500xa0μg/mL) or lower (20xa0μg/mL) concentration of MNPs was less efficient than that achieved at 100xa0μg/mL concentration. In conclusion, the relatively asymmetric morphological rod-shaped MNPs can kill cancer cells more effectively than spherical MNPs when being exposed to AMF by virtue of their mechanical oscillations.

Added value of SPECT/spiral CT versus SPECT in diagnosing solitary spinal lesions in patients with extraskeletal malignancies.

PurposeThe aim of this study was to investigate the added value of single-photon emission computed tomography (SPECT)/spiral computed tomography (CT) versus SPECT alone in the differential diagnosis of solitary spinal lesions in patients with extraskeletal malignancies. Materials and methodsA total of 90 patients who had a solitary spine ‘hot spot’ that could not be definitively diagnosed using planar scintigraphy were enrolled in the study. SPECT/spiral CT was performed on the indeterminate lesions in the spine. Images were independently interpreted by two experienced nuclear medicine physicians. Each spinal lesion was graded on a four-point diagnostic scale (1, benign; 2, likely benign; 3, likely bone metastasis; 4, bone metastasis). The final diagnosis of each lesion was based on pathological confirmation or follow-up. &kgr; scores were used to evaluate inter-reviewer agreement and agreement of the SPECT and SPECT/spiral CT diagnoses with the final diagnosis. ResultsFinal diagnoses revealed 25 bone metastases and 65 benign lesions. Forty percent (36/90) of the solitary spinal lesions were diagnosed as equivocal (likely benign or likely bone metastasis) according to SPECT, whereas only 5.6% (5/90) were diagnosed as equivocal according to SPECT/spiral CT. For SPECT/spiral CT-based and SPECT-based diagnoses, the &kgr; scores for inter-reviewer agreement were 0.889 (P<0.001, 95% confidence interval 0.824–0.954) and 0.504 (P<0.001, 95% confidence interval 0.401–0.607). The diagnostic accuracies of SPECT/spiral CT and SPECT images were 91.1% (82/90) and 58.9% (53/90), respectively (&khgr;2=24.919, P<0.001). ConclusionCompared with SPECT imaging alone, SPECT/spiral CT imaging was more accurate and valuable in the differential diagnosis of solitary spinal lesions in patients with extraskeletal malignancies.

18F-radiolabeled GLP-1 analog exendin-4 for PET/CT imaging of insulinoma in small animals.

BackgroundInsulinoma is a neuroendocrine tumor derived from the &bgr; cells of pancreatic islets. They are usually relatively inaccessible for surgical intervention. High expression levels of glucagon-like peptide-1 (GLP-1) receptor have been detected in insulinoma. AimThe aim of the study was to evaluate the potential of 18F-radiolabeled GLP-1 analog exendin-4 for the diagnosis of insulinoma using PET/computed tomography imaging. Materials and methodsThe GLP-1 receptor-specific molecular probe [18F]FB-exendin-4 was prepared by the conjugation of exendin-4 and N-succinimidyl-4-[18F] fluorobenzoate ([18F]SFB). High expression of GLP-1 by the RIN-m5f insulinoma line and GLP-1 receptor specificity were evaluated by determining the saturation curve for in-vitro binding of 125I-radiolabeled exendin-4 and by investigation of the competitive binding between 125I-radiolabeled and unlabeled exendin-4. Further, the in-vivo biodistribution and micro-PET/computed tomography images of insulinoma-bearing mice were studied. ResultsAn overall radiochemical yield of 35.6±2.3% (decay corrected, n=5) and specific radioactivity of around 30 GBq/µmol were achieved for [18F]FB-exendin-4, and the radiochemical purity was over 98%. Both in-vitro and in-vivo studies confirmed the specificity of [18F]FB-exendin-4 to insulinoma cells. Conclusion[18F]FB-exendin-4 has been found to be an effective molecular imaging probe for detecting insulinomas.

Study on the Distribution and Elimination of the New Hormone Irisin In Vivo: New Discoveries Regarding Irisin

Irisin is a newly discovered factor that is secreted by skeletal muscle and plays an important role in the homeostasis and metabolism of energy balance. This study used irisin radiolabeled with (125)I and small-animal SPECT/CT imaging to investigate the metabolic elimination and distribution of irisin in vivo. Irisin was labeled with (125)I using the Iodogen method. Small-animal SPECT/CT imaging was performed on C57/B16 mice at 15, 30, 60, 120, and 240u2009min after receiving a tail vein injection, and the radioactive distribution in the organs of mice was determined at 15, 60, and 120u2009min. Small-animal SPECT/CT imaging revealed the highest level of radioactivity in the gallbladder followed by the liver and kidney. Radioactivity decreased gradually with time in all organs. The radioactive distribution in the mice organs also showed that the highest %ID/g was in the gallbladder followed by the kidney and liver, and decreased gradually with time. The radioactivity in the gastric system reached its highest level at 60u2009min. Finally, our study showed the metabolic clearance of (125)I-irisin is achieved primarily through the hepatobiliary and renal system and provided the basis for the clinical application of irisin.

Breast-specific gamma imaging with Tc-99m-sestamibi in the diagnosis of breast cancer and its semiquantitative index correlation with tumor biologic markers, subtypes, and clinicopathologic characteristics.

ObjectivesTo determine the sensitivity of breast-specific gamma imaging (BSGI) in diagnosing breast cancer and assess the potential correlation between the semiquantitative index of BSGI and biologic markers, molecular subtypes, and clinicopathologic characteristics of breast cancer. Materials and methodsThe sensitivity of BSGI for breast cancer was retrospectively assessed in 102 female breast cancer patients who underwent BSGI before surgery and was compared with that of ultrasonography and mammography. BSGI was visually graded on the basis of the Society of Nuclear Medicine and Molecular Imaging guideline. Tracer uptake in the cancer as the lesion to nonlesion ratio (L/N) was calculated semiquantitatively and was subsequently correlated to tumor biologic markers, molecular subtypes, and clinicopathologic characteristics. ResultsThe sensitivity of BSGI for breast cancer by visual analysis was 94.1% (96/102) in our cohort, which was 100% (47/47) in the subgroup of patients with a tumor size more than 2.0u2009cm and 89.1% (49/55) in the subgroup of patients with a size less than or equal to 2.0u2009cm. The sensitivity of BSGI was significantly higher than that of ultrasonography of 84.2% (85/101) (P=0.022) and mammography of 84.5% (60/71) (P=0.037). There was no significant correlation between the L/N and expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and antigen Ki-67, and the subtypes or histologic grade of the cancer (P>0.05). However, the value of L/N was associated with infiltration degree (P=0.005), axillary lymph node status (P=0.029), and tumor size (P=0.002). Multivariate analysis further indicated that the value of L/N was correlated with infiltration degree (P=0.016) and tumor size (P=0.002). ConclusionBSGI has a high sensitivity for detecting primary breast cancer. The value of L/N on BSGI was independently related to infiltration degree and tumor size of breast cancer, but not to expression of tumor receptor markers and histologic grade.

Design and preliminary assessment of 99mTc-labeled ultrasmall superparamagnetic iron oxide-conjugated bevacizumab for single photon emission computed tomography/magnetic resonance imaging of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has a very high incidence and mortality. Early diagnosis and timely treatments are therefore required to improve the quality of life and survival rate of HCC patients. Here, we developed a vascular endothelial growth factor (VEGF)-based multimodality imaging agent for single photon emission computed tomography (SPECT), computed tomography (CT) and magnetic resonance imaging (MRI) and used it to assess HCC mice and explore the combinative value of CT/MRI-based morphological imaging and SPECT functional imaging. HCC targeting with 125I-labeled bevacizumab monoclonal antibody (mAb) was examined using SPECT/CT in HepG2 tumor-bearing mice after intravenous mAb injection. Based on this, an integrated, bimodal, VEGF-targeted, ultrasmall superparamagnetic iron oxide (USPIO)-conjugated 99mTc-labeled bevacizumab mAb was synthesized to increase tumor penetration and accumulations. The in vivo pharmacokinetics and HepG2 tumor targeting were explored through in vivo planar imaging and SPECT/CT using a mouse model of HepG2 liver cancer. The specificity of the radiolabeled nanoparticles for HepG2 HCC was verified using in vitro immunohistochemistry and Prussian blue staining. With diethylenetriamine pentaacetic acid as a bifunctional chelating agent, USPIO-bevacizumab achieved a 99mTc labeling efficiency of >90xa0%. The in vivo imaging results also exhibited the targeting of USPIO on HepG2 HCC. The specificity of these results was confirmed using in vitro immunohistochemistry and Prussian blue staining. Our preliminary findings showed the potential of USPIO as an imaging agent for the SPECT/MRI of HepG2 HCC.

The combined effects of serum lipids, BMI, and fatty liver on 18F-FDG uptake in the liver in a large population from China: an 18F-FDG-PET/CT study.

ObjectivesThe aim of the study was to investigate the combined effects of serum lipids, BMI, and fatty liver on the liver uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). MethodsA total of 676 individuals were retrospectively studied. The mean standardized uptake value (SUV) was used to quantify liver 18F-FDG uptake. Univariate analyses and multivariate regression models identified variables that predicted the mean liver SUV before and after dichotomizing participants into low and high BMI groups. ResultsThe mean liver SUV (1.831±0.417) differed significantly among nutritional categories (P=0.005) and degrees of fatty liver (P<0.001). An increase in mean liver SUV was noted in individuals with mild and moderate fatty liver compared with normal individuals and in overweight individuals compared with underweight individuals, whereas a downward trend was identified in both individuals with severe fatty liver and those who were obese. BMI had the strongest association with severity of fatty liver (r=0.443, P<0.001). Triglyceride, HDL, apolipoprotein-A, age, and BMI were independent variables predicting liver SUV mean in the whole population, whereas fatty liver severity presented as an independent variable only in the low BMI population (P=0.031). ConclusionBMI, age, triglyceride, HDL, and apolipoprotein-A were independent variables predicting liver 18F-FDG uptake. Mild and moderate degree of fatty liver had a positive effect on liver 18F-FDG uptake, whereas a severe degree of fatty liver negatively affected 18F-FDG uptake. Attention should be paid to liver metabolism in patients with fatty liver before using liver as the comparator in determining focal 18F-FDG uptake elsewhere within the abdomen.

The value of (18)F-FDG PET/CT in the diagnosis of uterine intravenous leiomyomatosis extended into the right atrium.

Intravenous leiomyomatosis (IVL) of the uterus is a rare neoplasm which usually occurs after hysterectomy. Due to its rarity and non-specific clinical manifestations, IVL is commonly misdiagnosed as malignant thrombus or thrombosis and treated inappropriately. Herein, we report an unusual case of a 51 years old woman with IVL without hysterectomy or abdominal manifestations. The IVL was detected in the right atrium. This case highlights the usefulness of (18)F-FDG PET/CT in the diagnosis of IVL.

The Imaging of Insulinomas Using a Radionuclide-Labelled Molecule of the GLP-1 Analogue Liraglutide: A New Application of Liraglutide

Objective This study explores a new, non-invasive imaging method for the specific diagnosis of insulinoma by providing an initial investigation of the use of 125I-labelled molecules of the glucagon-like peptide-1 (GLP-1) analogue liraglutide for in vivo and in vitro small-animal SPECT/CT (single-photon emission computed tomography/computed tomography) imaging of insulinomas. Methods Liraglutide was labelled with 125I by the Iodogen method. The labelled 125I-liraglutide compound and insulinoma cells from the INS-1 cell line were then used for in vitro saturation and competitive binding experiments. In addition, in a nude mouse model, the use of 125I-liraglutide for the in vivo small-animal SPECT/CT imaging of insulinomas and the resulting distribution of radioactivity across various organs were examined. Results The labelling of liraglutide with 125I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (Kd) was 128.8±30.4 nmol/L(Nu200a=u200a3), and the half-inhibition concentration (IC50) was 542.4±187.5 nmol/L(Nu200a=u200a3). Small-animal SPECT/CT imaging with 125I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125I-liraglutide treatment, the target/non-target (T/NT) ratio for tumour and muscle tissue was 4.83±1.30(Nu200a=u200a3). Our study suggested that 125I-liraglutide was predominantly metabolised and cleared by the liver and kidneys. Conclusion The radionuclide 125I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.

A Novel Ideal Radionuclide Imaging System for Non-invasively Cell Monitoring built on Baculovirus Backbone by Introducing Sleeping Beauty Transposon

Sleeping Beauty (SB) transposon is an attractive tool in stable transgene integration both in vitro and in vivo; and we introduced SB transposon into recombinant sodium-iodide symporter baculovirus system (Bac-NIS system) to facilitate long-term expression of recombinant sodium-iodide symporter. In our study, two hybrid baculovirus systems (Bac-eGFP-SB-NeoR and Bac-NIS-SB-NeoR) were successfully constructed and used to infect U87 glioma cells. After G418 selection screening, the Bac-eGFP-SB-NeoR-U87 cells remained eGFP positive, at the 18th and 196th day post transfection (96.03u2009±u20090.21% and 97.43u2009±u20090.81%), while eGFP positive population declined significantly at 18 days in cells transfected with unmodified baculovirus construct. NIS gene expression by Bac-NIS-SB-NeoR-U87 cells was also maintained for 28 weeks as determined by radioiodine uptake assay, reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot (WB) assay. When transplanted in mice, Bac-NIS-SB-NeoR-U87 cells also expressed NIS gene stably as monitored by SPECT imaging for 43 days until the tumor-bearing mice were sacrificed. Herein, we showed that incorporation of SB in Bac-NIS system (hybrid Bac-NIS-SB-NeoR) can achieve a long-term transgene expression and can improve radionuclide imaging in cell tracking and monitoring in vivo.