Design, synthesis and biological evaluation of novel estrogen-derived steroid metal complexes.

A new series of estrogen-derived metal complexes were synthesized and characterized. The functionalized estrogen receptor ligands were prepared by a four-step synthetic strategy, and then three transition metal Pd, Ni, Zn were introduced readily to give the title metal complexes, in which the squaramide was introduced as ion acceptor for the first time in the development of estrogen-derived metal complexes for estrogen receptor. Upon binding to estrogen receptors, all of the estrogen conjugates exhibited acceptable binding affinity (up to 4.

Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography in monitoring the response of breast cancer to neoadjuvant chemotherapy: a meta-analysis.

Introduction: To evaluate the diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in monitoring the response of breast cancers to neoadjuvant chemotherapy.

Methods: Articles published in medical and oncologic journals between January 2000 and June 2012 were identified by systematic MEDLINE, Cochrane Database for Systematic Reviews, and EMBASE, and by manual searches of the references listed in original and review articles. Quality of the included studies was assessed by using the quality assessment of diagnosis accuracy studies score tool.

An in vitro and in vivo evaluation of a reporter gene/probe system hERL/(18)F-FES.

Purpose: To evaluate the feasibility of a reporter gene/probe system, namely the human estrogen receptor ligand binding domain (hERL)/16α-[(18)F] fluoro-17β-estradiol ((18)F-FES), for monitoring gene and cell therapy.

Methods: The recombinant adenovirus vector Ad5-hERL-IRES-VEGF (Ad-EIV), carrying a reporter gene (hERL) and a therapeutic gene (vascular endothelial growth factor, VEGF165) through an internal ribosome entry site (IRES), was constructed. After transfection of Ad-EIV into bone marrow mesenchymal stem cells (Ad-EIV-MSCs), hERL and VEGF165 mRNA and protein expressions were identified using Real-Time qRT-PCR and immunofluorescence.

Tyrosinase as a multifunctional reporter gene for Photoacoustic/MRI/PET triple modality molecular imaging.

Development of reporter genes for multimodality molecular imaging is highly important. In contrast to the conventional strategies which have focused on fusing several reporter genes together to serve as multimodal reporters, human tyrosinase (TYR)--the key enzyme in melanin production--was evaluated in this study as a stand-alone reporter gene for in vitro and in vivo photoacoustic imaging (PAI), magnetic resonance imaging (MRI) and positron emission tomography (PET). Human breast cancer cells MCF-7 transfected with a plasmid that encodes TYR (named as MCF-7-TYR) and non-transfected MCF-7 cells were used as positive and negative controls, respectively.

Therapeutic gene expression in transduced mesenchymal stem cells can be monitored using a reporter gene.

Aim: We constructed a recombinant adenovirus construct Ad5-sr39tk-IRES-VEGF(165) (Ad5-SIV) that contained a mutant herpes viral thymidine kinase reporter gene (HSV1-sr39tk) and the human vascular endothelial growth factor 165 (VEGF(165)) gene for noninvasive imaging of gene expression. The recombinant adenovirus Ad5-SIV was transfected into rat bone marrow-derived mesenchymal stem cells (MSCs), and we measured the expression of HSV1-sr39tk and VEGF(165) to evaluate the feasibility of monitoring VEGF(165) expression using reporter gene expression.

Methods: The MSCs were infected with Ad5-SIV at various levels of infection (MOI), ranging from 0 to 100 infectious units per cell (IU/cell).

A multimodality reporter gene for monitoring transplanted stem cells.

Introduction: The aim of this study is to explore the feasibility of a triple-fused reporter gene, termed TGF [herpes simplex virus type 1 thymidine kinase (HSV1-tk), enhanced green fluorescent protein (eGFP) and firefly luciferase (Fluc)], to monitor stem cells using multimodality molecular imaging.

Methods: A recombinant adenovirus vector carrying the triple-fused reporter gene (Ad5-TGF) was constructed. Bone marrow mesenchymal stem cells (BMSCs) were transfected with different virus titers of Ad5-TGF [multiplicities of infection (MOIs) were 0, 50, 100, 150, 200 and 250].

Correlation of clinicopathological features and expression of molecular markers with prognosis after ¹³¹I treatment of differentiated thyroid carcinoma.

Purpose: The aim of this study was to identify molecular markers associated with differentiated thyroid carcinoma (DTC) patients and to determine whether there was a correlation between clinicopathological features or molecular markers and the outcome of radioiodine therapy.

Patients And Methods: We retrospectively reviewed the records of 68 patients with papillary thyroid carcinoma (PTC) and 6 patients with follicular thyroid carcinoma (FTC), who underwent iodine treatment. All patients were divided into a cured group (no evidence for disease) and a noncured group (presence of residual or recurrent disease).

Fully automatic synthesis of [¹⁸F]FES for reporter gene hERL expression imaging.

We have developed a fully automatic method for the synthesis of 16α-[¹⁸F]fluoroestradiol ([F]FES) using a TRACERlab FXFN module. Following [¹⁸F]fluorination, the intermediate was hydrolyzed with a mixture of 2 N HCl in acetonitrile (CH3CN) and then neutralized with sodium bicarbonate (NaHCO3). After HPLC purification, the decay-corrected radiochemical yield of [¹⁸F]FES was 50 ± 2.

A novel technique for the preparation of (125)I-5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl) uracil [correction of urail] and its biodistribution pattern in Kunming mice.

In this study, a novel technique for the preparation of (125)I-5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FIAU) was developed, (125)I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FTAU) was labeled with radioiodine ((125)I). A rotary evaporation method was used to remove excess methanol.

Comparison of rNIS and hNIS as reporter genes for noninvasive imaging of bone mesenchymal stem cells transplanted into infarcted rat myocardium.

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.

A highly effective bifunctional ligand for radioimmunotherapy applications.

A novel bifunctional ligand (3p-C-NETA) for antibody-targeted radioimmunotherapy (RIT) of β-emitting radioisotopes (90)Y and (177)Lu was efficiently synthesized via an unexpected regiospecific ring opening of an aziridinium ion. 3p-C-NETA instantly formed a very stable complex with (90)Y or (177)Lu. 3p-C-NETA is an excellent bifunctional ligand for RIT.

Novel human single chain antibody fragments that are rapidly internalizing effectively target epithelioid and sarcomatoid mesotheliomas.

Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with (⁹⁹m)Tc ((⁹⁹m)Tc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. (⁹⁹m)Tc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68% to 92% internalized within 1 hour.

The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma.

Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with (111)In ((111)In-IL-M1), along with control non-targeted liposomes ((111)In-CL).

[Study of infective efficiency of two adenovirus vectors to rBMSC and its mechanism].

Objective: To investigate the infective efficiency of Ad5/EGFP versus AdF35/EGFP to rat bone marrow mesenchymal stem cells (rBMSC) and understand its mechanism.

Methods: rBMSC were isolated from rat bone marrow by density gradient method. The expressions of CD90, CD29, CD44, CD34, CD11b and CD45 on the surface of rBMSC were measured by flow cytometry.

Autoradiography study and SPECT imaging of reporter gene HSV1-tk expression in heart.

Aim: To demonstrate the feasibility and optimal conditions of imaging herpes simplex virus 1-thymidine kinase (HSV1-tk) gene transferred into hearts with (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ((131)I-FIAU) using autoradiography (ARG) and single photon emission computed tomography (SPECT) in animal models.

Methods: HSV1-tk inserted into adenovirus vector (Ad5-tk) and adenovirus (Ad5-null) was prepared. Rats or rabbits were divided into a study group receiving intramyocardial injection of Ad5-tk, and a control group receiving Ad-null injection.

Targeting prostate cancer cells in vivo using a rapidly internalizing novel human single-chain antibody fragment.

Unlabelled: Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human antibody fragment, a small-size platform, to provide high contrast in a mouse model of human prostate carcinoma.

Methods: A prostate tumor-targeting single-chain antibody fragment (scFv), UA20, along with a nonbinding control scFv, N3M2, were labeled with (99m)Tc and evaluated for binding and rapid internalization into human prostate tumor cells in vitro and tumor homing in vivo using xenograft models.

[Autoradiography reporter gene (Ad5-tk carrying HSV1-tk gene) expression imaging in rat myocardium].

Objective: Radionuclide imaging of reporter gene expression holds promise for noninvasive monitoring of gene therapy. Herpes simplex virus 1-thymidine kinase (HSV1-tk) has been successfully applied to the tumor tissue.We explored the feasibility of the expression imaging of HSV1-tk reporter gene in rat myocardium by using SPECT reporter probe (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ((131)I-FIAU) and autoradiography (ARG).

[Myocardial single photon emission tomography imaging of reporter gene expression in rabbits].

Objective: To explore the feasibility of single photon emission computed tomography (SPECT) detection of heart reporter gene expression and observed the optimal transfecting titer and imaging time by using herpes simplex virus 1-thymidine kinase (HSV1-tk) as reporter gene and 131I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (131I-FIAU) as reporter probe in rabbit myocardium.

Methods: The recombinant Ad-tk carrying HSV1-tk gene and adenovirus (Ad) as vector was constructed and intramyocardially injected to rabbits at various concentrations (1 x 10(9) pfu, 5 x 10(8) pfu, 1 x 10(8) pfu, 5 x 10(7) pfu, 1 x 10(7) pfu). Two days later, rabbits were injected with 600 microCi 131I-FIAU in ear-margin vein and then underwent SPECT myocardium imaging for detection of HSV1-tk expression at 6 h, 24 h, 48 h and 72 h after injection, rabbits with 1 x 10(9) pfu Ad-tk injection were imaged at 96 h and 120 h.

The antiproliferative effects of somatostatin receptor subtype 2 in breast cancer cells.

Aim: Somatostatin receptor subtype 2 (SSTR2) is the principal mediator of somatostatin's (SST) antiproliferative effects on normal and cancer cells. Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit the proliferation of tumor cells, and, if so, the mechanisms that might be involved.

Methods: SSTR2 expression levels were determined by qRT-PCR in several tumor cell lines.

Comparative study of cellular kinetics of reporter probe [(131)I]FIAU in neonatal cardiac myocytes after transfer of HSV1-tk reporter gene with two vectors.

Aim: Reporter gene imaging is a promising approach for noninvasive monitoring of cardiac gene therapy. In this study, HSV1-tk (herpes simplex virus type 1 thymidine kinase) and FIAU (2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-iodouracil) were used as the reporter gene and probe, respectively. Cellular uptakes of radiolabeled FIAU of neonatal rat cardiac myocytes transferred with HSV1-tk were compared between two vectors, adenovirus and liposome.

[Feasibility of apoptosis-imaging agent 99mTc-HYNIC-annexin V in early assessment of chemotherapeutic effect on tumor models].

Objective: To evaluate if 99mTc-HYNIC-annexin V may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo.

Methods: Annexin V was labeled with 99mTc using HYNIC as a bifunctional agent. Normal Kunming mice received inoculation of Ehrlich ascites cells into the right upper limb.

(99m)Tc-YIGSR as a receptor tracer in imaging the Ehrlich ascites tumor-bearing mice as compared with (99m)Tc-MIBI.

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction.

A comparative study of 99mTc-YIGSR and 99mTc-MIBI uptake in tumor cells.

To investigate a new kind of tumor tracer 99mTc-YIGSR developed from a five amino structure (YIGSR) of the Laminin -chain, which can bind to the laminin receptors of tumor specifically, and radiolabeled with MAG3. (1) Preparation of the 99mTc-YIGSR probe: with S-Acetly-NH3-MAG3 as the chelator and with proper reductants YIGSR was labeled with 99mTc; (2) Cell culture and viability measurement: EAC was maintained in RPMI 1640 supplemented with calf serum; the trypan blue exclusion was applied to calculate the cell viability; (3) Study of the cell dynamic: The EAC's uptake of 99mTc-YIGSR and 99mTc-MIBI was observed at 37 degrees C and 22 degrees C, respectively. (1) The labeling efficiencies of 99mTc-YIGSR and 99mTc-MIBI were (62 +/- 3)% and (96 +/- 2)%, respectively; (2) The cell viability was declined with time of incubation; (3) At 37 degrees C, the EAC'S uptake of 99mTc-YIGSR and 99mTc-MIBI reached the peak of (43.

Role of beta-adrenergic signal transduction pathway on myocardial ischemic preconditioning of rats.

To study the changes in every part of the beta-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1+, 2+, 3+ groups according to preconditioning procedure.