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.

Synthesis and biological evaluation of [131I]iodocarvedilol as a potential radiopharmaceutical for heart imaging.

The optimization of the radiolabeling yield of carvedilol with iodine-131 was described. Dependence of the labeling yield of [131I]iodocarvedilol on the concentration of carvedilol, chloramine-T content, pH of the reaction mixture and reaction time was studied in details. Carvedilol was labeled with iodine-131 at pH 6 with a labeling yield of 92.6 ± 2.77% by using 100 µg carvedilol, 200 µg chloramin-T (CAT) and 30 min reaction time. The formed [131I]iodocarvedilol was nearly stable for a time up to one day. Biodistribution of [131I]iodocarvedilol was investigated in experimental animals. [131/123I]iodocarvedilol was located in the heart with a concentration of 19.6 ± 0.41% of the injected dose at 60 min post injection. It has a high heart uptake and heart to liver ratio, both of which are beneficial for high-quality SPECT (single-photon emission computerized tomography) myocardial imaging. [131/123I]iodocarvedilol solve most the drawbacks of the FDA (Food and Drug Administration) approved 99mTc-sestamibi.