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.
Jasanada
F
F
Faculté de Pharmacie, Université Paul Sabatier, Toulouse, France.
Urizzi
P
P
Souchard
J P
JP
Le Gaillard
F
F
Favre
G
G
Nepveu
F
F
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002850:Chromatography, Gel; D004355:Drug Stability; D019786:Gadolinium DTPA; D006801:Humans; D007202:Indicators and Reagents; D007205:Indium Radioisotopes; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D016719:Radioimmunodetection; D011869:Radioligand Assay; D011973:Receptors, LDL / Q000378:metabolism; D013228:Stearates; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D007205:Indium Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D013228:Stearates; C077628:gadolinium stearylamide DTPA; C099575:indium DTPA-bis(stearylamide); D004369:Pentetic Acid; D019786:Gadolinium DTPA