Enzymatic Synthesis of Uracil Glucuronide, Labeling with ^125/131I, and In Vitro Evaluation on Adenocarcinoma Cells

Abstract

Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% +/- 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled (125/131)I-UNG and (125/131)I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of (125/131)I-UOG were higher than those of (125/131)I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of (125/131)I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I-125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages.

Radioiodine labeled CdSe/CdS quantum dots: Lectin targeted dual probes

“…It has been used to label various biomolecules [14][15][16][17][18] such as proteins, peptides, and antibodies [19,20]. Regarding with Lec, V. Album agglutinin [21], phytohemagglutinin-L [22], and Viscum album agglutinin-I Lec [21] were labeled with 125 I via iodogen method to show receptor ligand interactions.…”

Synthesis of radioiodinated thymoquinone glucuronide conjugated magnetic nanoparticle (¹²⁵i-tqg-fe₃o₄) and its cytotoxicity and in vitro affinity

“…Labeling glucuronide derivatives with technetium-99m ( 99m Tc) or radioiodine with the advantage of higher expression of beta glucuronidase enzymes in tumor tissues rather than normal tissues, have been studied by our group for more than a decade 1,2,4,5,[8][9][10][11]13,15,16,21,[23][24][25][26][27]29,30 .…”