Glycol-Chitosan-Based Technetium-99m-Loaded Multifunctional Nanomicelles: Synthesis, Evaluation, and In Vivo Biodistribution

Abstract

We hereby propose the use of stable, biocompatible, and uniformly sized polymeric micelles as high-radiotracer-payload carriers at region-of-interest with negligible background activity due to no or low offsite radiolysis. We modified glycol chitosan (GC) polymer with varying levels of palmitoylation (P) and quaternization (Q). Quaternary ammonium palmitoyl glycol chitosan (GCPQ) with a Q:P ratio of 9:35 (Q9P35GC) offers >99% biocompatibility at 10 mg mL−1. Q9P35GC micelles exhibit >99% 99mTechnetium (99mTc) radiolabeling via the stannous chloride reduction method without heat. The 99mTc-Q9P35GC micelles (65 ± 3 nm) exhibit >98% 6 h serum stability at 37 °C and 7 day of radiochemical stability at 25 °C. HepG2 cells show a higher uptake of FITC-Q9P35GC than Q13P15GC and Q20P15GC. The in vivo 24 h organ cumulated activity (MBq h) order follows: liver (234.4) > kidneys (60.95) > GIT (0.73) > spleen (88.84). The liver to organ ratio remains higher than 2.4, rendering a better contrast in the liver. The radiotracer uptake decreases significantly in fibrotic vs. normal liver, whereas a blocking study with excess Q9P35GC significantly decreases the radiotracer uptake in a healthy vs. fibrotic liver. FITC-Q9P35GC shows in vivo hepato-specific uptake. Radiotracer liver uptake profile follows reversible binding kinetics with data fitting to two-tissue compartmental (2T), and graphical Ichise multilinear analysis (MA2) with lower AIC and higher R2 values, respectively. The study concludes that 99mTc-Q9P35GC can be a robust radiotracer for noninvasive hepatocyte function assessment and diagnosis of liver fibrosis. Furthermore, its multifunctional properties enable it to be a promising platform for nanotheranostic applications.

Keywords

• glycol chitosan
• radiotracers
• technetium-99m radiolabeling
• polymeric micelles
• biocompatible
• noninvasive imaging