Cancer is one of the main causes of death for human beings. Clinical oncologists increasingly rely upon imaging for diagnosis, stage, response assessment, and follow-up in cancer patient. However, 18F-FDG is not a tumor specific agent, inflammation and infection also have intensive uptake of 18F-FDG, resulting in false positive diagnosis, and some tumors have low uptake of 18F-FDG or even do not uptake 18F-FDG, leading to false negative diagnosis. So it is urgent to develop non-18F-FDG novel tumor targeting agent. Recently, a large number of researches in vitro have demonstrated that berberine has anti-tumor activity against a variety of tumor cells by inducing tumor cell apoptosis through inhibition of mitochondrial respiratory chain etc. So far, there is no credible evidence of berberine targeting in tumor in vivo. We proposed a hypothesis that berberine has the characteristics of tumor targeting biodistribution in vivo, and verified the proposal by 18F-berberine PET/CT imaging in VX2 muscle tumor-bearing rabbit model. In this review, we intend to give an overview of the progress of berberine anticancer, the structural bases of berberine anticancer and the uderlying molecular mechanisms of berberine anticancer indentified so far. We also introduce the first visualization of 18F labeled berberine derivatives targeting tumor in VX2 muscle tumor-bearing rabbit model by PET/CT. These breakthrough findings suggest that 18F-berberine derivatives as a potential PET/CT tumor targeted molecular imaging agent may have important implications for cancer targeting therapy, molecular imaging and modernization of Traditional Chinese Medicine.
Berberine ; chemistry ; Fluorodeoxyglucose F18 ; chemistry ; Humans ; Molecular Imaging ; Neoplasms ; diagnosis ; Positron-Emission Tomography ; Tissue Distribution ; Tomography, X-Ray Computed

Objective To discuss the clinical application of laparoscopic ultrasound (LUS) in laparoscopic nephron sparing surgery(NSS) for central renal tumors.Methods Eighteen patients underwent laparoscopic NSS for central renal tumors.The use of LUS was mainly lay in observing the nature and size of the tumor, the minimum distance from the tumor to capsule, collective system and renal artery, tumor's vasa vasorum,tumor localization and determination of margins.Results Of the 18 central renal tumors,the size was 11 - 29 mm,23.3 mm in average.The minimum distance from the tumor to capsule was 2 - 11mm,4.7 mm in average.The minimum distance within 5 mm to collective system and to capsule was 12 and 10 cases respectively.The tumor was surrounded by nephridial tissue completely on LUS, without protruding capsule.LUS diagnosis of 18 central renal tumors: 10 cases of renal angiomyolipoma,7 cases of renal cell carcinoma, 1 case of renal cyst with capsule wall calcification (at first diagnosed as renal carcinoma by CT).The findings of LUS were same to pathologic and(or) postoperative diagnoses.The accuracy of ultrasound localization was 100％.The surgical margins of 7 cases of renal cell carcinoma were all negative.Conclusions It is of high clinical value of LUS on locating the tumor and defining tumor margins in laparoscopic resection of central renal tumors.Besides, more information on tumor and vessel supply will be achieved.

Objective To investigate the utility of serum prostate specific antigen(PSA) density (PSAD),prostate antigen transition zone density(PSAT) and the ratio of free/total PSA with PSAD [(F/T)/PSAD] in the diagnosis of prostatic carcinoma (PCa) by three-dimensional ultrasonography.Methods Seventy-eight patients (serum prostate-specific antigen between 4-20 μg/L ) were involved.The prostatic volume and its transition zone volume were measured by three-dimensional ultrasonography.Then the relative parameters of PSA [PSAD,PSAT and (F/T)/PSAD] were calculated.Pathologic types were determined by using needle biopsy of prostate.Results Among them,27 patients were suffering from PCa,while the other 51 benign prostate hypertrophy (BPH).The difference of PSAD,PSAT and (F/T)/PSAD between PCa and BPH had arrived statistical significance (P<0.05).Proportions under the PCa curves were 0.736,0.760,0.800 respectively.Considering both sensitivity and specificity,a cutoff was recommanded:PSAD>0.20,PSAT>0.33,(F/T)/PSAD<0.8.Conclusions When the serum PSA level is between 4 μg/L and 20 μg/L,PSAD,PSAT and (F/T)/PSAD are of significant value to differentiate PCa from benign prostatic hyperplasia patients.The data are more reliable if prostatic volume are calculated by three-dimensional transrectal ultrasonography.

For the past decade, the diagnosis and treatment of coronary artery disease (CAD) has shifted from the traditional model by evaluating coronary artery stenosis with morphological imaging methods to a novel model by focusing on the detection of ischemia for risk stratification. The myocardial perfusion imaging (MPI) using stress single photon emission computed tomography (SPECT) has become the most commonly used stress imaging technique for the diagnosis and treatment of patients with suspected or known CAD. It has got strong supports, including those of the American College of Cardiology, American Heart Association, American Society of Nuclear Cardiology (ACC/AHA/ASNC) and other numerous clinical guidelines. They all stressed that the SPECT MPI is recommended to be used as the "gate keeper" to coronary angiography in order to prevent unnecessary intervention test and save the cost. However, in China the introduction and application of nuclear cardiology was late and highly unbalanced. This leads to the lack of understanding of nuclear cardiology in some clinicians, and there often is misunderstanding on correct selection of coronary angiography, cardiac CT, CT coronary angiography and others for diagnosis and treatment of CAD which results in a trend of over-application of these traditional techniques. In this article, we will focus on the status of nuclear cardiology, including SPECT, positron emission tomography (PET) MPI in the patients with CAD for the diagnosis of ischemia, risk stratification and management decision-making, and also compare it with the traditional morphological imaging techniques. In addition, we will briefly introduce the recent advances in cardiac hybrid imaging and molecular imaging. The aim of this paper is to popularize the knowledge of nuclear cardiology, and promote the rational application of nuclear cardiology in China.
Animals ; Cardiology ; methods ; trends ; Coronary Artery Disease ; diagnosis ; Humans ; Molecular Imaging ; Myocardial Perfusion Imaging ; Nuclear Medicine ; methods ; trends ; Tomography, Emission-Computed, Single-Photon ; methods

Objective To investigate the efficacy and safety of different optimal therapy strategies for hepatits B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients with suboptimal response to peginterferon-α-2a (peg-IFN-α-2a) at 24 weeks.Methods This open-label,single-center and prospective clinical observational study was conducted in Department of Infectious Diseases at Shanghai Changhai Hospital between January 2009 and December 2011.The cases of HBeAg-positive CHB with suboptimal response to peg-IFN-α-2a at week 24 were enrolled.Based on virological markers and patient preference,patients were treated with either peg-IFN-α-2a add-on adefovir dipivoxil (ADV) or switch-to telbivudine (LdT).Hepatitis B virus (HBV) virological and serological data were collected at week 12,24 and 48 after the initiation of optimal therapy.Adverse reactions were also monitored.Therapeutic efficacy was compared between two groups of patients before and after treatment by x2 test.Kruskall Wallis test and Mann-Whitney test were used for analysis of continuous variables.Results Among 193 HBeAg positive CHB patients treated with interferon,67 had suboptimal response and were enrolled.Forty five cases received peg IFN-α-2a add-on ADV treatment and 22 cases received switch-to LdT treatment.After 48 weeks of optimized therapy,the total tBeAg seroconversion rate was 25.3 ％.The rates of HBeAg loss,HBV DNA negative and alanine aminotransferase normalization were 26.8％,73.1％ and 83.5％,respectively.The peg-IFN-α-2a switch-to LdT strategy had better HBV DNA inhibition efficiency compared with the peg-IFN-α-2a add-on ADV strategy at week 12,24 and 48 (P=0.00,0.00 and 0.01,respectively).However,there was no significant difference of HBV DNA negative rate between two groups at week 48 (x2 =0.01,P=0.89).The obviously intolerable adverse reaction was not reported in two optimized strategy groups.Conclusions The 48-week optimized treatment for HBeAg positive CHB with suboptimal response to peg-IFN-α-2a at week 24 could achieve a higher HBeAg seroconversion rate.The switch-to LdT strategy may have better HBV DNA inhibition efficiency.Both strategies show satisfactory safety and tolerance.

Objective To evaluate the preoperative T staging value of rectal carcinoma by using double contrast-enhanced ultrasonography (DCUS).Methods 71 patients with rectal carcinoma were examined by ultrasound after infusing contrast agent and bolus injection of SonoVue preoperatively.The border,shape and perfusion patterns of the tumor were observed.After surgery,the T staging made by DCUS and perfused contrast-enhanced ultrasonography (PCUS) was compared with final pathologic results respectively.Results The accuracy of PCUS and DCUS in determining the T stage of rectal carcinoma were 71.8％(T1 72.7％％,T250.0％,T374.4％,T476.9％) and 85.9％(T190.9％,T275.0％,T387.1％,T484.6％) respectively.The difference between these two methods was statistically significant (P ＜0.05).Conclusions DCUS is a new valuable method for T staging of rectal carcinoma with its high accuracy preoperatively.

ObjectiveTo investigate the effects of the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17) in patients with chronic hepatitis B virus (HBV) infection.MethodsThe serum concentration of Treg/Th17 differentiation-related cytokines in 34 patients with chronic hepatitis B (CHB),20 patients with HBV related acute on chronic liver failure (ACHBLF),and 20 healthy controls (NC) were measured by enzyme-linked immunosorbent assay (ELISA) and proportion of peripheral Th17 and Treg cells were analyzed by flow cytometry.Numeration data was analyzed by Fisher's exact propability method and measurement data was tested by one-factor analysis of variance or Turkey multiple comparison.Results The levels of Th17 differentiation-related cytokines,II-1β (3.97±2.85) pg/mL,IL-6 (12.75±-8.87) pg/mL,and IL-21 (360.0±335.7) pg/ mL in patients with ACHBLF were significantly increased than those in NC,which were (1.87 ±0.94) pg/mL(q=4.559,P＜0.01),(5.28±0.72) pg/mL(q=7.309,P＜0.01) and (46.68±20.17) pg/mL(q=6.946,P＜0.01 ),respectively.The proportion of Th17 increased markedly in patients with ACHBLF than that in NC(q=3.972,P＜0.05).However,compared to NC and patients with ACHBLF,the Treg differentiation-related cytokine,TGF-β,in patients with CHB,increased significantly (q=4.536 and 5.323,respectively; both P＜0.01).And the population of Treg also increased markedly in CHB patients.The level of IL-17A which was the characteristic effector cytokine of Th17 was the highest in patients with ACHBLF.The peripheral Th17 cell proportion was positively correlated with the level of serum total bilirubin in patients with ACHBLF (γ=0.74,P＜0.01).Conclusions Th17 and Treg imbalance including cytokine profiles and cell numbers exists in patients with chronic HBV infection.The Th17 are active in patients with ACHBLF and Treg are active in patients with CHB.

Objective To investigate the role of double contrast-enhanced ultrasonography (DCUS) in the diagnosis of rectal gastrointestinal stromal tumors (GISTs). Methods In eleven patients with rectal GISTs before surgery, gastrointestinal ultrasound contrast agent were injected into rectal lumen and tumor’s two dimensional ultrasound features were analyzed. Microbubbles were injected into the vein to investigate the feature of lesion microcirculation perfusion. After the surgery, according to the tumor diameter and mitotic count, rectal GISTs were classified as very low-risk, low-risk, intermediated-risk and high-risk tumors. The very low-risk and low-risk tumors were grouped together as one group while the intermediated-risk and high-risk tumors were grouped together as another group. According to ultrasound performance and pathological type, ultrasonic features of rectal GISTs with different risk levels were estimated. Results Among all rectal GISTs cases, 63.6%(7/11) were low-risk. Under DCUS, the tumor diameter was less than 5 cm, with regular round, hypoechogenicity, uniform low enhancement and less internal liquefaction necrosis. For the 36.4%(4/11) high-risk cases, under DCUS, the tumor diameter was≥5 cm, with irregular round or lobulation, mixed hyperechogenicity and hypoechogenicity, nonuniform high enhancement, large blood vessel and common liquefied necrosis region. The biological behavior of rectal GISTs was relevant to lesion size, liquefaction necrosis and enhancement mode of ultrasound contrast and irrelevant to the bound and shape of lesion. The accuracy of DCUS and contrast-enhanced ultrasonography were 90.9%(10/11) and 72.7%(8/11) respectively. Conclusions DCUS is considered as an effective tool in diagnosingrectal GISTs and can get useful information of the biological characteristics. It has great value for the diagnosis and treatment of rectal GISTs.

This study was performed to explore the feasibility of antisense imaging with radiolabeled antisense oligonucleotides DNA in tumored nude mice in vivo. Two different tumor cell lines, KB-G2 and KB-31,were used; both antisense and control sense DNAs were administrated intratumorally. The hybridization activities analysis of MAG3 conjugated DNAs oligonucleotides was demonstrated by Polyacrylamide Gel Electrophoresis. The whole body imaging was performed 22 h after administration of radiolabeled antisense and control sense DNAs at 1.0 microg DNAs (100 microCi) in 100 microl per animal. Then the animals were sacrificed at 24 h after administration and the organs and tissues were dissected and weighed; the radioactivity of each sample was detected by r-counter; injection dose percentage per gram tissue (%ID/g) was calculated and the biodistribution obtained. Both MAGS conjugated oligonucleotides DNAs and natural oligonucleotides DNAs have the same hybridization activities. The whole body images demonstrate improved targeting of antisense DNAs vs sense DNAs in the KB-G2 but not the KB-31 animals. Tumor levels in the KB-G2 animals were significantly higher for the antisense DNAs vs sense DNAs (14.7 vs 8.5% ID/g) while this difference (8.6 vs 4.3% ID/g) was insignificant in the KB-31 animals. Evidence for tumor targeting in vivo by an antisense in that mechanism has been obtained; statistically higher tumor accumulations of the 99mTc-antisense DNA were observed when compared to the control 99mTc-sense DNA. The successful localization of antisense DNA in tumor demonstrates that antisense tumor targeting in vivo is feasible even though improvement in tumor delivery and normal tissue clearance are needed for practical antisense imaging.
Animals ; Carcinoma, Squamous Cell ; diagnostic imaging ; pathology ; Dipeptides ; Electrophoresis, Polyacrylamide Gel ; Female ; Mice ; Mice, Nude ; Mouth Neoplasms ; diagnostic imaging ; pathology ; Oligodeoxyribonucleotides, Antisense ; administration & dosage ; genetics ; Organometallic Compounds ; Radionuclide Imaging ; Tumor Cells, Cultured

The aim of this study is to explore the optimal labeling condition of technetium-99m labeled antisense oligonucleotides (ASON) DNA and sense oligonueleotides (SON) DNA against multi-drug resistance gene-1 (MIDR1) mRNA, to prepare its two-step icefrozen kits, and to perform the quality control of technetium-99m labeled ASON and SON DNAs and its two-step icefrozen kits. A 20 mer single-stranded ASON sequence and its SON sequence against MDR1 mRNA were synthesized respectively, both of the ASON and SON DNAs were uniform phosphorothioated for this investigation with a primary amine on the 5'-end via a six-carbon alkyl linker, and then were labeled with technetium-99m by conjugating with the bifunctional chelator S-Acetyl NHS-MAG3 to form ASON- and SON-MAC3 DNAs. The optimal labeling condition was explored by varying the amount of ASON- and SON-MAG3 DNAs, SnCl2.2H2O and buffer, the pH value in the reaction medium was also adjusted. The technetium-99m labeled ASON and SON DNAs' two-step icefrozen kits were developed. The radiochemical purities, labeling stability of ASON- and SON-MAG3 DNAs in vivo and vitro were measured, and stability of the two-step icefrozen kits were also studied. The recycled rates of ASON- and SON-MAG3 DNAs were over 70% (n >6), the two-step icefrozen kits of ASON- and SON-MAG3 DNAs were colourless ice crystal. The radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were over 92 %. The radiochemical purities were over 90% after stored at room temperature for 24 hours. The kits were stable within 6 months when stored at 0 degrees C, the radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were still over 90%. The two-step icefrozen kits of ASON- and SON-MAG3 DNAs were successfully developed. The radiochemical purities were all over 90%. The labeling method was simple, feasible and efficient with good stability.
Animals ; DNA, Antisense ; chemistry ; Isotope Labeling ; methods ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins ; chemistry ; pharmacokinetics ; Oligonucleotides, Antisense ; chemistry ; pharmacokinetics ; Radiopharmaceuticals ; chemical synthesis ; pharmacokinetics ; Random Allocation ; Technetium Tc 99m Mertiatide ; chemistry ; pharmacokinetics