Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effects of drugs and enhances the contrast between normal and pathologic tissues. One approach to achieve selectivity is to target overexpressed receptors on the membranes of tumor cells and to visualize the tumors by a noninvasive optical imaging method. Accordingly, we conjugated fluorescein and carbocyanine dyes to somatostatin and bombesin receptor-avid peptides and examined their receptor binding affinities. We also prepared potential dual imaging probes consisting of a bioactive peptide for tumor targeting, a biocompatible dye for optical imaging, and a radioactive or paramagnetic metal chelator for scintigraphic or magnetic resonance imaging of tumors. Using these approaches, the resulting carbocyanine derivatives of somatostatin and bombesin analogues retained high binding for their respective receptors. Further evaluation of representative molecules in rats bearing somatostatin- and bombesin-positive tumors showed selective uptake of the agents by the tumor cells. Unlike carbocyanine derivatives, the receptor binding of fluorescein-somatostatin peptide conjugates was highly sensitive to the type of linker and the site of fluorescein attachment on the nonreceptor binding region of the peptide. In general, the presence of flexible linkers disrupted binding affinity, possibly due to the interaction of the linker's thiourea group with the peptide's cyclic disulfide bond. While the receptor binding affinity of the dual probes was not dependent on the type of chelating group examined, it was affected by the relative positions of fluorescein and chelator on the lysine linker. For somatostatin compounds, best results were obtained when the chelator was on the alpha-amino lysine linker and fluorescein was on the epsilon-amino group. In contrast, conjugation of the chelator to epsilon- and fluorescein to the alpha-amino lysine linker of bombesin peptides resulted in high receptor binding. These findings indicate that despite their small size, conjugation of dyes to truncated somatostatin and bombesin peptide analogues results in promising diagnostic agents that retain high receptor binding activity in vitro. The results further show that these contrast agents can selectively and specifically localize in receptor-positive tumors in rat models.
Fluoroarenetricarbonylchromium(0) complexes were found to undergo Suzuki reactions with arylboronic acids to form biaryltricarbonylchromium(0) complexes in the presence of trimethylphosphine/palladium dibenzylideneacetone and caesium carbonate or caesium fluoride.
Carbon nanotubes (CNTs) have generated a tremendous amount of research interest because of their unique structural, electronic, magnetic, and mechanical properties. [1] Among the various synthetic methods employed for their preparation, chemical vapor deposition (CVD) has emerged to be most effective, and efforts are increasing in applying this technique to pre-growth device fabrication by utilizing (in particular lithographically) [2] patterned catalyst arrays and in situ tube assembly. [2,3] Crucial in this endeavor is the sitespecific batch production of ordered carbon with control of stoichiometry and ultimately morphology. One possible approach to achieving this would be the efficient thermal conversion of a defined, soluble, molecular organometallic precursor composed of both the carbon source and the metal catalyst, placed locospecifically by wetting and drying. Such a strategy would combine the advantages of the floating organometallic catalyst (for example, ferrocene, [Fe(CO) 5 ], etc.) CVD methodology [1d, 4] with a solid-state conversion of carbon precursors. Reports of the latter reveal some serious shortcomings with respect to yield and/or degree of graphitization, extremity of conditions, need for specialized equipment, the requirement of co-reagents, and simplicity of starting materials. [1d, 5] We have described the solid-state thermolysis of a [Co 2 (CO) 6 ]-complexed tetrabenzodehydro [20]annulene and some of its substructures to form ordered carbon material, but this method shared some of these drawbacks, in as much as the highest yields were only about 60 %. The desired product consisted of an (at best) approximately equal mixture of multiwalled tubes (MWNTs)
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