Synthesis and evaluation of radioiodinated cholesteryl ethers as lipoprotein probes

Abstract

Two novel cholesteryl ether derivatives were synthesized and radioiodinated: (1) [125I]cholesteryl m-iodobenzyl ether (125I-CIBE) and (2) [125I]cholesteryl 12-(m-iodophenyl)dodecyl ether (125I-CIDE). These radioiodinated ethers were incorporated into low-density lipoprotein (LDL) by incubating the compounds (solubilized in saline with Tween-20) with isolated LDL or with whole plasma. Such LDL preparations were taken up by cultured fibroblasts in a receptor-dependent manner similar to that of radioiodinated LDL. Upon injection into guinea pigs, 125I-CIBE-labeled guinea pig LDL cleared from the plasma similarly to radioiodinated guinea pig LDL. The primary sites of 125I-CIBE uptake were the adrenal and the liver, and the compound was stable to both hydrolysis and deiodination over 24 h. In summary, 125I-CIBE and 125I-CIDE, like previously described tritiated cholesteryl ethers, appear to be potentially useful tracers of cholesteryl ester uptake. Moreover, these radioiodinated probes have the advantage of being more easily quantitated in tissue samples as well as being detectable by noninvasive scintigraphic imaging.

Low-Density Lipoprotein as a Vehicle for Targeting Antitumor Compounds to Cancer Cells

“…The disadvantages can be low drug loading and leakage of drug from the complex, probably because some of it remains in the surface layer of the LDL and does not reach the core. LDL can be mixed directly with the drug (23,(93)(94)(95), with the drug as a dry film (96) (40 drug molecules/LDL can be incorporated but 78% is easily released in serum) (97), or with a drugcholesteryl ester microemulsion (88,89,98). Facilitated transfer (99) using natural transfer proteins has been tried (5, 100), giving 18 molecules/LDL (87).…”

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

“…18.4) [55]. Radioiodinated cholesteryl esters and hexaiodinated diglycerides are two such examples [63,64]. In addition, intercalation of amphiphilic metal chelating complexes, gallium-68 or indium-111 DTPA(stearylamide) (see Fig.…”

Comparison of methods for incorporating a radioiodinated residualizing cholesteryl ester analog into low density lipoprotein

“…Male guinea pigs (450-55Og) were anesthetized with xylazine (9mg) and ketamine (30mg), and the right carotid artery of each animal was cannulated essentially as described (Latham, 1977;DeForge et al, 1991). The radiolabeled guinea pig LDL preparations (1.1-8.6 pCi per animal) were then administered and blood samples (0.5 mL) were withdrawn via the cannula at 0.25, 0.5, 1, 2, 4 and 6 h post-injection from conscious, restrained animals (DeForge et al, 1991).…”