The aim of this study is to use new drugs capable of crossing the blood-brain barrier (BBB) to develop new radiopharmaceuticals for non-invasive brain imaging. Quetiapine (QTP) and cyclobenzaprine (CBP), as two 5-HT2A receptor antagonists, were successfully labeled with radioactive iodine (125I) using Chloramine-T (CAT) as an oxidizing agent via electrophilic substitution reactions. After studying the parameters affecting the labeling yield (substrate amount, CAT amount, pH of the reaction mix., reaction time and temperature), the highest radiochemical yields of125I-QTP and 125I-CBP were found to be 94.5 % ± 1.0 and 91.7 % ± 0.6, respectively, at pH 2. The biodistribution and the SPECT/CT image showed that the maximum uptake of radioiodinated-QTP by the mouse brain was 10.2% and 10.9% at 120 minutes post-injection, while the radioiodinated-CBP was 7.7% and 12.4% at 240 minutes post-injection. The results have shown that radioiodinated-QTP and radioiodinated-CBP are novel radiopharmaceuticals and may be used for brain imaging.