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One of the challenges facing superparamagnetic iron oxide (SPIO) nanoparticles is to improve their biological compatibility. While highly uniform SPIOs can be manufactured, the surfaces are hydrophobic as a result of the surfactants used in their fabrication. In this study, we developed a general strategy to fabricate an MR molecular imaging probe in one step by replacing hydrophobic surfactants with small peptides terminated with cysteine. The hydrophobic SPIO surface was transformed into a hydrophilic one by exchanging surface oleic acids with the peptides RGD-Cys or RGD-PEG-Cys. After the RGD-Cys and RGD-PEG-Cys peptide exchange, both RGD-Cys-SPIO and RGD-PEG-Cys-SPIO specifically targeted α β-expressing cells (A549) in vitro, with RGD-Cys-SPIO achieving this more efficiently. Furthermore, MR imaging of A549 tumors receiving RGD-Cys-SPIO or RGD-PEG-Cys-SPIO demonstrated that both the targeted particles could reach and label the α β-expressing tumor, much more efficiently than the non-targeted particles (Cys-SPIO). Histology showed that the probes not only target the tumor neovasculature but also extravasate from vessels and address the tumor cells. Our study shows that directly replacing oleic acid with cysteine or cysteine-terminated small peptides is a general strategy to transforming the hydrophobic surface of SPIO into a hydrophilic one, as well as providing targeting ligands. Such SPIOs are of interest as MR molecular imaging probes to detect for cancer in vivo. Copyright © 2010 John Wiley & Sons, Ltd. MR molecular imaging probe fabricated by cysteine-terminated small peptide replacement with oleic acid is able to target tumor cells in vitro as well tumor in vivo. [ABSTRACT FROM AUTHOR]

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 [SeSO32-] played an important role in the formation of CdSe QDs. The mechanisms about the influence factors were also presented. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: 2-Amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[18F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[18F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[18F]FPCV was −0.517. 6-[18F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5–18.8 times higher than that in wild-type cells. The plasma half-life of 6-[18F]FPCV was as follows: α t 1/2=1.2 min and β t 1/2=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[18F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression. [Copyright &y& Elsevier]

O-(2-[18F]fluoroethyl)- L-tyrosine ([18F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [18F]FET are similar to those of [18F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. [ABSTRACT FROM AUTHOR]

Abstract: 9-(4-Hydroxy-3-hydroxymethylbutyl) guanine (Penciclovir) is a potent and selective inhibitor of members of the herpes virus family. A new convenient synthesis of fluorinated Penciclovir analogues 9-(4-fluoro-3-hydroxymethylbutyl) guanine (FHBG) and 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-Fluoropenciclovir) were described. The structures of the products were characterized by UV, IR, 1H NMR, 19F NMR spectra and MS. [Copyright &y& Elsevier]

Elérh [ABSTRACT FROM AUTHOR]

6-[18F]Fluoro-L-Dopa (6-FDOPA) is the analogue of L-Dopa, the biosynthesis precursor for dopamine. As a PET tracer, it was widely applied for the presynaptic dopamine function studies in human brain. The application of a chiral phase-transfer-catalyst (PTC) in enantioselective synthesis of N.C.A. 6-[18F]Fluoro-L-Dopa has been developed recently. An improved procedure was described in this study. The labeling precursor (6-Trimethylammoniumveratraldehyde Triflate) and PTC (O-Allyl-N-(9)-anthracenylcinchonidinium Bromide) were synthesized. A successful synthesis route was developed for the preparation of 6-[18F]Fluoro-L-Dopa with high radiochemical yields (4-9%, decay uncorrected) and short synthesis time(80min). The radiochemical purity was over 99% and no D-isomer was detected by HPLC analysis using a chiral mobile phase. [ABSTRACT FROM AUTHOR]

S-benzoyl mercaptoacetyltriglycine (S-Bz-MAG3) was synthesized and labeled with carrier-free 188Re. The overall yield of S-Bz-MAG3 is higher than those published in the literature. Dependence of the labeling yield of 188Re-MAG3 upon concentration of reducing agent, pH, reaction time, and other parameters was examined and optimum conditions were obtained. The labeling yield of 188Re-MAG3 was more than 98%. The concentration procedure was succeeded with Sep-Pak C18 column to obtain highly concentrated 188Re-MAG3. The experimental conditions of labeling of IgG with carrier free 188Re via S-Bz-MAG3 as a bifunctional chelating agent (BFCA) by pre-radiolabeling of the chelate was studied. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results of this studiy may be useful for 188Re labeling of MAbs for radioimmunotherapy. [ABSTRACT FROM AUTHOR]

A method for 103Pd “molecular plating” onto the surface of the copper rod is reported. The optimal composition of the plating bath was: palladium chloride 2 g/l, ammonium hydroxide (28%) 150 ml/l, sodium hypophosphite 12 g/l, and ammonium chloride 37 g/l. The whole procedure of 103Pd “molecular plating” will last 50 minutes at 40 °C. This article provides valuable experience for the preparation of 103Pd seeds. [ABSTRACT FROM AUTHOR]

As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R8,15,21, L17]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [R8,15,21, L17]-VIP was produced with the radiochemical yield being as high as 33.6% ±3% (decay-for-corrected, n = 5) achieved within 100 min, a specific activity of 255 GBq/μmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [R8,15,21, L17]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor. [ABSTRACT FROM AUTHOR]

In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with 188Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl2·2H2O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 μl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study. [Copyright &y& Elsevier]

Abstract: Magnetic nanoparticles were synthesized, modified with polyacrylamide, and then characterized by TEM, FTIR, VSM and PCS. Rhenium-188 (188Re) was bound to the nanoparticles by imidazolyl groups of histidine immobilized on the surface. The labeling yield was about 90% with good in vitro stability. Such nanoparticles might be useful for magnetically targeted radiotherapy. [Copyright &y& Elsevier]

Purpose: This study evaluated the tolerance and therapeutic efficacy of rhenium-188 hydroxyethylidene diphosphonate ((188)Re-HEDP) in patients with different types of advanced cancer suffering from bone pain caused by osseous metastases., Methods: Sixty-four patients received a single injection of escalating doses of (188)Re-HEDP with various dosages. Vital signs were observed before and after treatment for 8 weeks; adverse effects and rebound pain were recorded within 8 weeks after injection. Blood counts, biochemical parameters, and electrocardiogram were also measured over a period of 8 weeks. Clinical follow-up studies including the bone pain score and the Karnofsky performance score were performed. Pain response was scored by a four-point pain-rating scale as complete, marked, mild, and no response., Results: No adverse effects or clinically significant changes in vital signs, electrocardiograms, and biochemical parameters in patients were observed, and there was no statistical change in alkaline phosphate levels in patients before or after treatment. The overall nadir of thrombopenia was at week 4, leucopoenia at week 3, and anemia at week 8. At week 8, the mean level of platelets and leukocytes returned to baseline levels. The pain score descended from 8.11 to 7.74 on the day of therapy, with a nadir of 4.89 at week 4, and up to 6.67 at week 8 after therapy (p < 0.05). The Karnofsky performance score continually increased from 74.81 before therapy to 82.31 at 8 weeks (p > 0.05 Pain palliation was reported by 73.33% of patients, with a mean duration of 6.85 weeks and a mean start time of 4.05 days. Of the specific tumor types, pain relief was achieved in 84.62% of patients with prostate cancer, 78.57% with breast cancer, 62.50% with lung cancer, and 55.56% with liver cancer., Conclusions: (188)Re-HEDP is a useful radiopharmaceutical agent for improving bone pain in patients with advanced cancer with painful bone metastases.

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.