Radiosynthesis and in silico bioevaluation of 131 I-Sulfasalazine as a highly selective radiotracer for imaging of ulcerative colitis

Abstract

This study demonstrated the tracking of ulcerative colitis, which is considered a stressful immune disease. Although there are many ways to test for this disease including dependence on gases, dyes, and painful anal endoscopy, these treatment modalities have many disadvantages. Hence, it is the utmost need of time to discover new methods to detect this chronic immune disease and to avoid the defects of traditional methodologies. Sulfasalazine (SSD) was labeled with iodine-131 (half-life: 8 days, Energy: 971 keV) under optimum reaction conditions including the amount of reducing agent, pH factor, chloramine-T (Ch-T) amount, and incubation period. Characterization was performed using ¹ H/ ¹³ C-NMR, ESI-MS, and HPLC (UV/ Radio) techniques. The biodistribution study was performed in normal and ulcerative mice models, and in silico molecular docking study was performed to evaluate the possible mechanism of action to target peroxisome proliferator-activated receptor gamma (PPARγ). The high radiolabeling yield of [¹³¹ I]-sulfasalazine ([¹³¹ I]-SSD) was achieved ≥90% through the direct labeling method with radioactive iodine-131 in the presence of chloramine-T (100 μg). The radiotracer [¹³¹ I]-SSD was observed to be stable in normal saline and freshly eluted serum up to 12 hr at ambient temperature (37℃ ± 2℃). The radiotracer [¹³¹ I]-SSD showed the highest uptake in the targeted organ (i.e., ulcerative colon) which was observed to be ≥75% injected dose per gram (% ID/g) organ for 24 hr postinjection (p.i). Furthermore, in silico data collected from molecular modeling analysis of SSD and [¹³¹ I]-SSD with antimicrobial protein (PDB code: 3KEG) and peroxisome proliferator-activated receptor gamma (PPARγ) (PDB code: 4XTA) showed azoreductase activity and high binding potential for PPAR-γ site, respectively. The results of biological studies obtained in this study enlighten the usefulness of radiotracer [¹³¹ I]-SSD as a potential imaging agent for ulcerative colitis.

Keywords: Azoreductase; [131I]-Sulfasalazine; chronic immune disease; peroxisome proliferator-activated receptor gamma; ulcerative colitis.