I-trazodone: preparation, quality control and in vivo biodistribution study by intranasal and intravenous routes as a hopeful brain imaging radiopharmaceutical.

OBJECTIVES

The preparation of I-trazodone hydrochloride and its biological evaluation as a promising brain imaging radiopharmaceutical using two routes of administration.

MATERIAL AND METHODS

Trazodone (TZ) was radiolabelled with I using direct electrophilic substitution, and different factors affecting labelling yield were studied. Quality control of I-TZ was carried out using ascending paper chromatography, paper electrophoresis, and high pressure liquid chromatography (HPLC). In vivo biodistribution of I-TZ was evaluated in Swiss albino mice using 3 methods: intravenous I-TZ solution (IVS), intranasal I-TZ solution (INS), and intranasal I-TZ microemulsion (INME).

RESULTS

Optimum labelling yield of 91.23±2.12% was obtained with in vitro stability of I-TZ up to 6h at room temperature. The biodistribution results showed a notably higher and sustained brain uptake for INME compared to IVS and INS at all time intervals. In addition, heart and blood uptake levels for INME were lower than those for IV solution which, in turn, could decrease the systemic side effects of trazodone. Also, the I-trazodone INME brain uptake of 6.7±0.5%ID/g was higher than that of Tc-ECD and Tc-HMPAO (radiopharmaceuticals currently used for brain imaging).

CONCLUSION

I-trazodone formulated as INME could be used as a promising radiopharmaceutical for brain imaging.