Duanzhi Yin

Superparamagnetic magnetite nanocrystal clusters: a sensitive tool for MR cellular imaging

Silica coated, PEI and citric acid hybrid superparamagnetic magnetite nanocrystal clusters (SMNC) were synthesized using either a mini-emulsion/sol-gel method or a polyol technique. After careful characterization of the size, structure, composition, and magnetic properties, the as-synthesized SMNC were used for cell labeling while the MR detection sensitivity of cells labeled with silica SMNC was performed with a 3 T whole body MR scanner. TEM investigations revealed that the sizes of the SMNC were about 200 nm and the SMNC mainly consisted of magnetite nanoparticles imbedded in a PEI, citric acid or polystyrene scaffold. Silica and citric acid SMNC were highly negatively charged and PEI SMNC were positively charged. Relaxometry measurements revealed that these SMNC possessed a very high MR sensitivity (silica SMNC: r(2) = 299 s(-1) mM(-1), PEI SMNC: r(2) = 124 s(-1) mM(-1)), especially for the citric acid SMNC (r(2) = 360 s(-1) mM(-1)). Furthermore, when used for cell (RAW264.7 cells) labeling, the SMNC had no adverse effect on cell viability, and the cell uptake of the SMNC show a dose- and time-dependent feature. MR imaging of cells labeled with silica SMNC indicated that cells with a concentration as low as 10 x 10(3) cells ml(-1) could be detected with a 3 T MRI scanner. Our study demonstrated that superparamagnetic magnetite nanocrystal clusters are a sensitive tool for cell imaging.

Radiolabeling and in vitro and in vivo Characterization of [18F]FB‐[R8,15,21, L17]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors

In an effort to develop a peptide‐based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R8,15,21, L17]‐VIP peptide for 18F‐labeling. This peptide inhibited 125I‐VIP binding to rats lung membranes with high affinity [half‐maximal inhibitory concentrations (IC50) of 0.12 nm]. Additionally, [R8,15,21, L17]‐VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N‐succinimidyl 4‐[18F] fluorobenzoate as labeling prosthetic group, [18F]FB‐[R8,15,21, L17]‐VIP was obtained in >99% radiochemical purity within 100 min in decay‐for‐corrected radiochemical yield of 33.6 ± 3% (n = 5) and a specific radioactivity 255 GBq/μmol at the end of synthesis. Stability of [18F]FB‐[R8,15,21, L17]‐VIP in vitro and in vivo were investigated. Biodistribution of this trace was carried out in mice with induced C26 colorectal tumor. Fast clearance of [18F]FB‐[R8,15,21, L17]‐VIP from non‐target tissues and specific uptakes by tumors realized higher tumor‐to‐muscle ratio (3.55) and tumor‐to‐blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [18F]FB‐[R8,15,21, L17]‐VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.

Radiolabelling of poly(histidine) derivatized biodegradable microspheres with the 188Re tricarbonyl complex [188Re(CO)3(H2O)3]+

ObjectivesMany radiopharmaceuticals have been studied as radiation synovectomy agents. In this study, we developed a new potential agent for radiation synovectomy: poly(lactic acid)–histidine (PLA–his) microspheres radiolabelled with [188Re(CO)3(H2O)3]+. MethodsThe reaction conditions for the chelation of [188Re(CO)3(H2O)3]+ and the radiolabelling of PLA microspheres were optimized and the stabilities for both steps tested in vitro. ResultsThe chelation efficiency of [188Re(CO)3(H2O)3]+ reached 93.12±1.82% with >95% radiochemical purity once the colloidal and free 188Re were removed by a small Sep-Pak column (Plus QMA). More than 90% of radioactivity stayed in the [188Re(CO)3(H2O)3]+ form over 5 h. The radiolabelling efficiency of PLA–his microspheres with [188Re(CO)3(H2O)3]+ was above 92%. After 3 days incubation at 37°C in calf serum, more than 80% of the radioactivity was still bound to the microspheres. ConclusionSuch microspheres are potentially useful as a radiation synovectomy agent for the treatment of chronically inflamed arthritic joints. Furthermore, they might be valuable in cancer brachytherapy.

Optimized Synthesis and Fluorescence Spectrum Analysis of CdSe Quantum Dots

An optimized synthesis route was applied for controlling the preparation of CdSe quantum dots (QDs) in an aqueous solution. Some key factors which influencing the properties of CdSe QDs, such as initial pH, stabilizers, ratio of precursor, etc. were investigated. The size, shape, crystal structure, and optical property of CdSe QDs were also characterized by TEM, XRD, UV-Vis, and fluorescence (FL) spectra. The result showed that high-quality cubic CdSe QDs with 3 nm were obtained. The experiments also confirmed that thioglycolic acid (TGA), under the conditions of weak acid, is a better stabilizer than others. The ratio of [Cd2+] to [SeSO3 2−] played an important role in the formation of CdSe QDs. The mechanisms about the influence factors were also presented.

Remote-controlled module-assisted synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine as tumor PET tracer using two different radiochemical routes

Abstract The positron-emitter fluorine-18 labeled amino acid O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) has shown very promising perspectives for brain tumor diagnosis with positron emission tomography (PET). There have been two existing preparation routes of [ 18 F]FET named direct nucleophilic radiofluorination of protected L-tyrosine and radiofluoroalkylation of unprotected L-tyrosine, respectively. A general module was designed specifically for the routine synthesis of [ 18 F]FET, which could be suitable for the present two chemical methods with simple modifications. The fluorinated intermediates and the final product were separated and purified using solid phase extraction (SPE) on the Sep-Pak silica plus cartridge instead of the time-consuming high performance liquid chromatography (HPLC) procedures. The total synthesis time was about 50–60 min with good radiochemical yield (about 20–40%, no-decay-corrected) and good radiochemical purity (more than 97%) for both the synthetic methods.

Radiosynthesis of 18F-(R8,15,21, L17)-vasoactive intestinal peptide and preliminary evaluation in mice bearing C26 colorectal tumours.

BackgroundRadiolabelled vasoactive intestinal peptide (VIP) and its analogues have shown their potential as imaging agents for diagnosing tumours expressing VIP receptor. However, the fast proteolytic degradation in vivo has limited their clinical use. AimTo prepare the 18F-labelled (R8,15,21, L17)-VIP analogue in a convenient way and to evaluate its potential as an imaging agent for VIP receptor-positive tumours. MethodsRadiolabelled (R8,15,21, L17)-VIP was obtained by conjugation with N-succinimidyl 4-([18F]fluoromethyl) benzoate and purified by HPLC. Radiochemical purity and specific radioactivity were measured by analytical HPLC. In-vitro stability of the product was carried out in HSA solution and analysed by HPLC. Biodistribution study was carried out in mice bearing C26 colorectal tumours. Results18F-(R8,15,21, L17)-VIP was obtained in greater than 99% radiochemical purity within 60 min in decay-for-corrected radiochemical yields of 21.8±4.7% (n=5) and a specific activity of 17.76 GBq · μmol−1 at the end of synthesis (EOS). Results of in-vitro studies demonstrated a high stability in human serum albumin (HSA) solution. Biodistribution data showed a rapid blood clearance and specific binding towards receptor-positive tumours. Conclusion18F-(R8,15,21, L17)-VIP was prepared by a convenient method. Preliminary biodistribution results showed its potential for imaging tumours over-expressing VIP receptors and encouraged further investigation.

Syntheses of two potential dopamine D4 receptor radioligands : 18F labelled chromeno[3,4-c]pyridin-5-ones

Summary The dopamine D4 receptor is hypothesized to relate with the pathophysiology and pharmacotherapy of schizophrenia while its level in brain regions is much lower and to date no suitable tracer is available for the study of D4 receptor in vivo . Therefore, selective imaging agents for the D4 subtype are badly needed. Based on the structure-activity analysis of chromeno[3,4-c]pyridin-5-ones as dopamine D4 receptor ligands, two fluorine-18 labelled chromeno[3,4-c] pyridin-5-one derivatives, 3-(4-[18F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one and 3-(4-[18F]fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one were synthesized through a two-step one-pot method. Their radiochemical yields were around 19.7% (decay-corrected) and radiochemical purities were higher than 95% with specific activities of about 120 GBq/μmol.

Applied radioactivity in radiation synovectomy with [188Re]rhenium sulfide suspension.

BackgroundEarly experience demonstrated absorbed dose in radiation synovectomy is about 100 Gy. For reaching this dose, the applied radioactivity should be calculated. MethodTwenty-nine synovitic models of rabbit were treated by intra-articular injection of [188Re]rhenium sulfide and histological changes of synovium and cartilage were examined. The applied radioactivity was calculated by method of absorbed dose factor. In clinical, eleven haemophilic patients with haemarthrosis were performed radiation synovectomy with treated [188Re]rhenium sulfide. The synovial thickness was evaluated by MR and its value was used to calculate the applied radioactivity. After radiation synovectomy, all patients were followed up by synovial thickness, regional inflammation, and clinical course including bleeding frequency. ResultsIn rabbit models, the synovitic membrane can be eliminated by calculated radioactivity as planed without damaging the joint cartilage. In patients study, all patients exhibited significant reductions in synovial thickness and inflammation after radiation synovectomy with the planed radioactivities of [188Re]rhenium sulfide. Post-procedure bleeding frequency reduction in excellent and good reached to 63.6% by 18 months. In the cases of joint bleeding, the need for antihaemophilic factor treatment decreased immensely. Most of the recurrent episodes of bleeding were mild, subsiding with local means. ConclusionThe applied radioactivity in radiation synovectomy could be calculated according to thickness of inflamed synovium. Further study including comparison therapeutic results from calculated individual activities with results from fixed activities and long-term follow-up is warranted.

Radiolabeling RGD peptide and preliminary biodistribution evaluation in mice bearing S180 tumors.

ObjectiveTo prepare the rhenium-188 (188Re)-arginine-glycine-aspartic acid (RGD) peptide in a convenient manner and to evaluate its potential as an agent for &agr;v&bgr;3 integrin receptor-positive tumors. MethodsRadiolabeled RGD was obtained by conjugating the His group at the end of peptide with fac-[188Re(H2O)3(CO)3]+. Chelating efficiency of fac-[188Re(H2O)3(CO)3]+ and radiolabeling efficiency of radiolabeled peptide were measured by thin-layer chromatography and high-performance liquid chromatography. In-vitro stability of the radio-complex was determined in phosphate-buffered saline (0.05mol/l, pH 7.4), new-born calf serum, His or Cys solution at 37°C or room temperature and analyzed by thin-layer chromatography. A biodistribution study was carried out in mice bearing S180 tumors. Results188Re-RGD was obtained with a more than 95% of radiolabeling efficiency, and showed high stability in phosphate-buffered saline, new-born calf serum, His and Cys solution. Furthermore, this radio-complex was cleared rapidly from the blood and showed specific tumor uptake in mice bearing S180 tumors. Conclusion188Re-RGD was prepared by a simple method. Preliminary biodistribution results showed its potential as an agent for cancer therapy and encouraged further investigation.

Relationship between the flavonoid composition and flower colour variation in Victoria

Victoria (Nymphaeaceae), an annual or perennial aquatic plant genus, contains only two species: V. amazonica (Poepp.) J. C. Sowerby and V. cruziana A. D. Orb. Both species have large floating leaves and variable flower colour. Both Victoria species are night bloomers, which have white petals on the first blooming night that then turn pink or ruby red on the second blooming day. The mechanism of the colour change of Victoria petals during anthesis is still unclear. In this study, flavonoids in Victoria petals of both species were evaluated and quantified by high-performance liquid chromatography with photodiode array detection (HPLC-DAD) and by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) for the first time. In total, 14 flavonoids were detected in Victoria petals, including 4 anthocyanins and 10 flavonols. The flavonoid compositions differed across the two species, resulting in different colours between the inner and outer petals. With increased anthocyanin content across blooming days, the colour of Victoria flowers changed over time. The results of this study will improve understanding of the chemical mechanism of colour formation and lay the foundation for selective colour breeding in Victoria.