An antioxidant sinapic acid ester isolated from Iberis amara.

The isolation of 6-O-sinapoyl sucrose (1) from Iberis amara seeds and an evaluation of its antioxidative properties in comparison with sinapic acid and ascorbic acid are reported.

Internalization of indium-labeled LDL through a lipid chelating anchor in human pancreatic-cancer cells as a potential radiopharmaceutical for tumor localization.

Low-density lipoproteins (LDL) labeled with indium via a lipid-chelating agent, the bis(stearylamide) of diethylenetri-aminepentaacetic acid (L), were evaluated as a potential radiopharmaceutical (111In-L-LDL) for tumor localization by studying their internalization in human pancreatic cancer cells (Capan-1). Using Dil-LDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate-LDL), this cell line was shown to bind human LDL with a high-affinity saturable component and a low-affinity non-saturable (40%) component. The single saturable high-affinity binding site had a KD of 27.5 +/- 2.1 micrograms/ml and a maximal binding of 610 +/- 7.5 ng/ml protein. Electron-microscopic examination of the In-L-LDL particles revealed the peripheral distribution of the electron-dense indium atoms at the outer surface of LDL. The modified LDL were then shown to be internalized by the cells. After conjugation of In-L-LDL to colloidal gold to follow the different stages of internalization, electron-microscopic examination showed that the In-L-LDL gold conjugates were stuck to the external sheet of the plasma apical and microvilli membrane, into earlier and later endosomes and into multivesicular bodies, suggesting the penetration of the In-L-LDL particles into lysosomal vacuoles. The observation of In-L-LDL-gold conjugates in deep-seated cytoplasm suggests that LDL could be employed as a drug-transport vehicle for targeting cytotoxics or radionuclides close to the cell nucleus.

Indium-111 labeling of low density lipoproteins with the DTPA-bis(stearylamide): evaluation as a potential radiopharmaceutical for tumor localization.

In order to use the LDL receptor pathway to target radionuclides to cancer sites for imaging and diagnostic purposes, a labeling procedure of LDL with 111In using the DTPA-bis(stearylamide) (L) has been developed. This bifunctional ligand is intended to be incorporated into the phospholipid monolayer of LDL and to specifically chelate the In3+ cation at the surface. The ligand was incorporated into LDL in buffered medium with a 65-80% yield. The L-LDL samples are stable over a 24 h period when examined by dialysis, allowing their storage before indium-111 radiolabeling. In vitro studies of In-L-LDL particles show that indium labeling is rapidly achieved (1 h). More than 85% of the indium atoms are bound to the chelating functions of the incorporated DTPA derivatives and less than 10% to the nonspecific complexation sites of LDL (e.g., protein residues). After incubation in human serum, the indium activity recovered in the LDL fraction of In-L-LDL samples (95%) is much higher than in In-LDL samples (35%), pointing out the strong stabilizing chelating effect of the ligand. Competitive binding studies show that In-L-LDL are recognized by LDL receptors of A549 cells like native LDL when the In-L/LDL ratio varies from 5 to 30. All these in vitro experiments demonstrate that the In-L-LDL conjugates possess properties suitable for further work with in vivo experiments.