Preparation and evaluation of radiolabeled gliclazide parenteral nanoemulsion as a new tracer for pancreatic ß-cells mass.

PURPOSE: The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing ß-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the ß-cells of the pancreas. METHODS: Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated in silico and in vivo in normal and diabetic rats. RESULTS AND CONCLUSIONS: The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of -45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic ß-cells.

Preparation and evaluation of radioiodinated avanafil: A novel potential radiopharmaceutical for the diagnostic evaluation of erectile dysfunction.

Avanafil, a selective second-generation phosphodiesterase-5 inhibitor, was successfully labeled with iodine-125 via electrophilic and different factors affecting the labeling efficiency were studied. The labeled compound exhibited in-vitro stability of more than 24 h with a maximum labeling yield of up to 98.4 ± 1.9 %. Molecular modeling and in-vitro assessment of tracer inhibitory activity were performed to ensure that radiolabeling did not affect its binding ability to the target. Biodistribution studies were performed in normal rats and models of erectile dysfunction. The tracer specifically accumulated in the penis, and the clearance appeared to take place via the hepatobiliary route. Results suggested the usefulness of radiolabeled avanafil as a promising tracer for erectile dysfunction.