99mTc-3PRGD2 scintigraphy to stage liver fibrosis and evaluate reversal after fibrotic stimulus withdrawn.

OBJECTIVE: Scintigraphy using 99mTc-3PRGD2 targeting integrin αvß3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal. METHODS: Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point). Another 6 rats with 8-week TAA administration (the 8-week group) and 6 rats which were injected with TAA for 6 weeks, and then withdrawn of TAA for 2 weeks (spontaneous recovery rats, SRR) were designed. The ratios of radioactivity detected in the liver vs. the heart at 30 min post-injection of 99mTc-3PRGD2 (L/H30min), the collagen proportionate area (CPA), the protein and mRNA levels of integrin αv, integrin ß3 were analyzed and compared among groups. RESULTS: The Ishak stage scores of the livers in the control and 2, 4, 6-week groups increased when the TAA administration period was extended. L/H30min increased with the upgrading of liver fibrosis and the differences between each pair of groups were statistically significant (p 30 min in the 8-week group was similar to that in the 6-week group (p > 0.05), but was significantly higher than that in the SRR group (p = 0.005). CONCLUSIONS: Scintigraphy using 99mTc-3PRGD2 may provide a non-invasive method for grading liver fibrosis and assessing liver fibrosis reversal.

Investigation of aquaporins and apparent diffusion coefficient from ultra-high b-values in a rat model of diabetic nephropathy.

BACKGROUND: To assess kidney damage in a rat model of type-2 diabetic nephropathy based on apparent diffusion coefficient (ADC) data obtained from ultra-high b-values and discuss its relationship to the expression of aquaporins (AQPs). METHODS: This study was approved by the institutional Animal Care and Use Committee. Thirty male Sprague-Dawley rats were randomised into two groups: (1) untreated controls and (2) diabetes mellitus (DM). All rats underwent diffusion-weighted imaging (DWI) with 18 b-values (0-4500 s/mm2). Maps of low ADC (ADClow), standard ADC (ADCst) and ultra-high ADC (ADCuh) were calculated from low b-values (0-200 s/mm2), standard b-values (300-1500 s/mm2) and ultra-high b-values (1700-4500 s/mm2), respectively. The expression of AQPs in the kidneys was studied using immunohistochemistry. Laboratory parameters of diabetic and kidney functions, ADClow, ADCst, ADCuh, and the optical density (OD) of AQP expression in the two groups were compared using an independent t test. Correlations between ADCs and the OD of AQP expression were evaluated by Pearson's correlation analysis. RESULTS: ADCuh were significantly higher in the cortex (CO), outer stripe of the outer medulla (OS) and inner stripe of the outer medulla (IS), and the OD values of AQ-2 were significantly higher in the OS, IS and inner medulla (IM) in DM animals compared with control animals. ADCuh and OD values of AQP-2 expression were positively correlated in the OS, IS and IM of the kidney. CONCLUSIONS: ADCuh may work as useful metrics for early detection of kidney damage in diabetic nephropathy and may be associated with AQP-2 expression.

Quantitative assessment of early liver fibrosis in rats using 13N-NH3·H2O PET/CT.

OBJECTIVE: To investigate the value of N-NH3·H2O PET/computed tomography (CT) and the inhibitor, acetazolamide (ACZ), in the quantitative diagnosis of early liver fibrosis and the assessment of liver fibrosis stage. MATERIALS AND METHODS: Twenty-four male Wistar rats (293.54±37.99 g) were used in this study and grouped by pathology after biopsy. Using N-NH3·H2O as an imaging agent and ACZ as an aquaporin 1 inhibitor, the rats were subjected to a dynamic PET/CT scan for 45 min. According to data reconstruction and imaging analysis, we calculated the mean standard uptake value (SUVmean) of the liver at the time points of 20, 90 s, 5, 10, 15, 20, and 25 min. From the results of N-NH3·H2O, the liver SUVmean in the control group and the liver fibrosis model group at different time points were compared. In addition, blood perfusion, interstitial diffusion, and N-NH3·H2O metabolism of the two groups were compared. Single-factor analysis of variance was used to analyze the differences between the SUVs in the groups at any time point and the paired-sample t-test was used to compare the SUVs before and after addition of the inhibitor. RESULTS: We included four rats in the control group (S0) and 20 rats in the liver fibrosis group (which included early-stage S1: 11 rats, progressive-stage S2+S3+S4: nine rats). Three rats in S0, seven rats in S1, and six rats in S2+S3+S4 were paired. The SUVmean at 90 s was statistically different (P<0.05); however, the other groups showed statistical difference at all time points (P>0.05). After the addition of the inhibitor, ACZ, the SUVmean of S0 and S2+S3+S4 at 10, 15, 20, and 25 min was statistically different (P<0.05). CONCLUSION: N-NH3·H2O PET/CT may aid the diagnosis of liver fibrosis. N-NH3·H2O PET/CT combined with ACZ may help distinguish between the early stage and the progressive stage of liver fibrosis.

Preparation of magnetic resonance probes using one-pot method for detection of hepatocellular carcinoma.

AIM: To prepare the specific magnetic resonance (MR) probes for detection of hepatocellular carcinoma (HCC) using one-pot method. METHODS: The carboxylated dextran-coated nanoparticles were conjugated with anti-α-fetoprotein (anti-AFP) or anti-glypican 3 (anti-GPC3) antibodies through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS)-mediated reaction to synthesize the probes. The physical and chemical properties of the probes were determined by transmission electron microscopy (TEM) and dynamic light scattering, and the relaxivity was compared to uncombined ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) using a 1.5T clinical MR scanner. The binding efficiency of the antibodies to nanoparticles was measured with an ultraviolet-visible spectrophotometer. In addition, the probes were incubated with targetable cells in vitro. RESULTS: The superparamagnetic MR probes (anti-GPC3-USPION probe and anti-AFP-USPION probe) were synthesized using one-pot method. Their mean hydrodynamic diameter was 47 nm with a broader slight size distribution. The coupling efficiency of carboxylated dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) with anti-GPC3 or anti-AFP antibody was 15.9% and 88.8%, respectively. Each of the USPIO nanoparticles may bind 3 GPC3 antibodies or 12 AFP antibodies. The statistical analysis showed no significance (P > 0.05) in shortening the T1 and T2 values when comparing the USPIO-AFP or USPIO-GPC3 to USPIO. Analysis of TEM images revealed that anti-GPC3-USPION probes and anti-AFP-USPION probes could specifically enter into the HepG2 cell by combining with the GPC3 receptors or AFP receptors, whereas the HepG2 cell sample incubated with USPIONs showed no or few nanoparticles in the cytoplasm. CONCLUSION: The synthesized probes using one-pot method can be used for in vitro experimental study and have potential clinical application in MR imaging for detection of hepatocellular carcinomas.

[The research progress of SPECT/CT].

With the development of molecular imaging technology, incorporate multiple modes of medical imaging imaging techniques of SPECT/CT and PET/CT technology with a certain degree of development. But compared to SPECT/CT and PET/CT technologies, SPECT/CT far earlier than PET/CT technology to clinical applications, due to a variety of factors influence SPECT/CT far PET/CT clinical applications to grow faster. This article highlights the progress and problems of SPECT/CT technology.

Value of ¹8F-FDG PET/CT in the diagnosis of primary gastric cancer via stomach distension.

OBJECTIVE: To clarify the usefulness of (18)F-FDG PET/CT for detecting primary gastric cancer via gastric distention using a mixture of milk and Diatrizoate Meglumine. MATERIALS AND METHODS: A total of 68 patients (male: 47, female: 21; age: 41-87 years) suspected of gastric carcinoma underwent (18)F-FDG PET/CT imaging. After whole-body PET/CT imaging in a fasting state, the patients drank a measured amount of milk with Diatrizoate Meglumine. Local gastric district PET/CT imaging was performed 30 min later. The imaging was analyzed by semi-quantitative analysis, standardized uptake value (SUV) of the primary tumor was measured in a region of interest. The diagnosis results were confirmed by gastroscopy, pathology, and follow-up results. RESULTS: Of the 68 patients, 56 malignant gastric neoplasm patients (male: 37, female: 19) were conformed. The sensitivity, specificity, positive predictive value and negative predictive value of fasting whole-body PET/CT imaging for a primary malignant tumor were 92.9%, 75.0%, 94.5%, and 69.0%, respectively. The values for distension with a mixture of milk and Diatrizoate Meglumine were 91.1%, 91.7%, 98.1%, and 68.8%, respectively. The area under the curve was 0.919 ± 0.033 and 0.883 ± 0.066 for the diagnosis of gastric cancer with SUVmax in a fasting state and after intake of mixture respectively, the differences were not statistically significant (P=0.359). Using gastric distension with a mixture of milk and Diatrizoate Meglumine, the mean ratio of the lesion's SUVmax to the adjacent gastric wall SUVmax increased significantly from 3.30 ± 3.05 to 13.50 ± 15.05, which was statistically significant (P<0.001). CONCLUSIONS: (18)F-FDG PET/CT imaging is highly accurate for the diagnosis of primary gastric carcinoma. Gastric distention can display the lesions more clearly, however, it cannot significantly improve diagnostic accuracy.

99mTc-3PRGD2 for integrin receptor imaging of lung cancer: a multicenter study.

UNLABELLED: (99m)Tc-3PRGD2 is a new SPECT tracer targeting integrin α(V)ß(3) receptor for detecting tumors, imaging angiogenesis, and evaluating tumor response to therapy. A multicenter study was designed to investigate the efficacy of (99m)Tc-3PRGD2 for the evaluation of patients with lung cancer. METHODS: Seventy patients (51 men, 19 women; mean age ± SD, 63 ± 9 y) with a suspected lung lesion and for whom definite pathologic diagnosis was finally obtained (malignant, n = 58; benign, n = 12) were recruited from 6 centers. Whole-body planar scanning and chest SPECT were performed at 1 and 4 h, respectively, after intravenous injection of 11.1 MBq/kg (0.3 mCi/kg) of (99m)Tc-3PRGD2. The images were read in consensus by 6 experienced nuclear medicine physicians masked to the source, history, and pathologic diagnosis. The tumor-to-background (T/B) ratios were calculated for semiquantitative analysis. A Student t test was used for statistical analysis, and a P value less than 0.05 was considered significant. RESULTS: With low (99m)Tc-3PRGD2 background in the lungs and mediastinum, most lung malignancies were prominent on the 1-h images (T/B ratio, 1.65 ± 0.47 for the planar imaging and 2.78 ± 1.52 for SPECT). The T/B ratios were significantly lower in the benign lesions (P < 0.05). The sensitivity was 88% for semiquantitative analysis and could reach 93%-97% in visual analysis when considering the volume effect, necrosis, and metastasis. However, the specificity was only 58%-67%. Most lymph node and bone metastases could also be detected. CONCLUSION: (99m)Tc-3PRGD2 imaging at 1 h is sensitive for the detection of lung cancer, meriting further investigation of (99m)Tc-3PRGD2 as a novel clinical tracer for integrin receptor imaging.

A multicenter clinical trial on the diagnostic value of dual-tracer PET/CT in pulmonary lesions using 3'-deoxy-3'-18F-fluorothymidine and 18F-FDG.

UNLABELLED: Some new radiotracers might add useful information and improve diagnostic confidence of (18)F-FDG imaging in tumors. A multicenter clinical trial was designed to investigate the diagnostic performance of dual-tracer ((18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]) PET/CT in pulmonary nodules. METHODS: Fifty-five patients underwent dual-tracer imaging in 6 imaging centers using the same models of equipment and standardized protocols. The images were interpreted by a collective group of readers who were unaware of the clinical data. The diagnostic performance using either tracer alone or dual-tracers together, with or without CT, was compared. The histological diagnosis or clinical findings in a 12-mo follow-up period served as the standard of truth. RESULTS: In 16 patients with malignant tumor, 16 with tuberculosis, and 23 with other benign lesions, the sensitivity and specificity of (18)F-FDG and (18)F-FLT were 87.5% and 58.97% and 68.75% and 76.92%, respectively. The combination of dual-tracer PET/CT improved the sensitivity and specificity up to 100% and 89.74%. The 3 subgroups of patients could be best separated when the (18)F-FLT/(18)F-FDG standardized uptake value ratio of 0.4-0.90 was used as the threshold. CONCLUSION: By reflecting different biologic features, the dual-tracer PET/CT using (18)F-FDG and (18)F-FLT favorably affected the diagnosis of lung nodules.