Synthesis of Fluorine-18 Functionalized Nanoparticles for use as in vivo Molecular Imaging Agents

Nanoparticles containing fluorine-18 were prepared from block copolymers made by ring opening metathesis polymerization (ROMP). Using the fast initiating ruthenium metathesis catalyst (H_2IMes)(pyr)_2(Cl)_2Ru=CHPh, low polydispersity amphiphilic block copolymers were prepared from a cinnamoyl-containing hydrophobic norbornene monomer and a mesyl-terminated PEG-containing hydrophilic norbornene monomer. Self-assembly into micelles and subsequent cross-linking of the micelle cores by light-activated dimerization of the cinnamoyl groups yielded stable nanoparticles. Incorporation of fluorine-18 was achieved by nucleophilic displacement of the mesylates by the radioactive fluoride ion with 31% incorporation of radioactivity. The resulting positron-emitting nanoparticles are to be used as in vivo molecular imaging agents for use in tumor imaging

N-Terminal tagged lactate dehydrogenase proteins: evaluation of relative hydrophobicity by hydrophobic interaction chromatography and aqueous two-phase system partition

The hydrophobic contributions of 17 individual peptides, fused to the N-terminal of Bacillus stearothermophilus lactate dehydrogenase (LDH) were studied by hydrophobic interaction chromatography (HIC) and aqueous two-phase system (ATPS). The constructs were sequenced from a protein library designed with a five-amino acid randomised region in the N-terminal of an LDH protein. The 17 LDH variants and an LDH control lacking the randomised region were expressed in Escherichia coli. HIC and ATPS behaviour of the proteins indicated significant differences in protein hydrophobicity, even though the modifications caused only 1% increase in protein molecular weight and 2% variation in isoelectric points. HIC and ATPS results correlated well (R-2 = 0.89). Protein expression was clearly affected by N-terminal modification, but there was no evidence that the modification affected protein activity. A GluAsnAlaAspVal modification resulted in increased protein expression. In most cases, HIC and ATPS results compared favourably with those predicted on the basis of 34 amino acid residue hydrophobicity scales; assuming exposure of tag residues to solution. Exceptions included LeuAlaGlyValIle and LeuTyrGlyCysIle modifications, which were predicted, assuming full solution exposure, to be more hydrophobic than observed. (C) 2004 Elsevier B.V. All rights reserved

Prognostic factors for death after surgery for small intestinal neuroendocrine tumours.

Background: Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery. Methods: This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors. Results: In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy. Conclusion: Stage and symptomatic disease are important prognostic factors in SI-NET