IN-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 ca ncer sites for imaging and diagnostic purposes, a labeling procedure o f LDL with In-111 using the DTPA-bis(stearylamide) (L) has been develo ped. This bifunctional ligand is intended to be incorporated into the phospholipid monolayer of LDL and to specifically chelate the In3+ cat ion at the surface. The ligand was incorporated into LDL in buffered m edium with a 65-80% yield. The L-LDL samples are stable over a 24 h pe riod when examined by dialysis, allowing their storage before indium-1 11 radiolabeling. In vitro studies of In-L-LDL particles show that ind ium labeling is rapidly achieved(1 h). More than 85% of the indium ato ms are bound to the chelating functions of the incorporated DTPA deriv atives 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 mu ch higher than in In-LDL samples (35%), pointing out the strong stabil izing chelating effect of the ligand. Competitive binding studies show that In-L-LDL are recognized by LDL receptors of A549 cells like nati ve 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 properti es suitable for further work with in vivo experiments.