Radiolabeling, Chemical and Biological Evaluation of Some CNS Drugs for Some Nuclear Medicine Applications

More than 80% of radiopharmaceuticals used in nuclear medicine are ^99mTc-labeled compounds. The reasons for such an important position of ^99mTc are its short half life 6 h, 140-keV gamma-ray which is suitable for gamma camera and readily availability in a sterile, pyrogen-free, and carrier-free state from ⁹⁹ Mo–^99mTc generators. Iodine is one of the common halogens located in group VII in the periodic table which contains F, Cl, Br, I and At. There are 33 known isotopes of iodine, ¹¹⁰I to ¹⁴²I, all of them are radioactive except the naturally occurring ¹²⁷I which is stable. Among these 32 radioactive iodine isotopes, four are of special interest, namely ¹²³I, ¹²⁴I, ¹²⁵I and ¹³¹I. The aim of this thesis is to develop potential selective radiopharmaceuticals for the non-invasive brain imaging. Zaleplon, Trazodone labeled with ¹²⁵I and Carbamazepine labeled with ^99mTc (the three drugs which have the ability to cross blood-brain barrier) were successfully labeled and their biodistribution in mice was studied. In this thesis, the labeling of zaleplon and trazodone were carried out by direct iodination of zaleplon and trazodone (150 µg of each) with radioiodine in a fast single step at 40 and 25 ºC, respectively for 15 minutes. Chloramine-T (200 µg) was added to Zaleplon and Trazodone, respectively as an oxidizing agent .Also the ph of the reaction was adjusted to ph= 4 for Zaleplon and ph =7 for Trazodone. High radiochemical yields of Zaleplon (97 %) and Trazodone (99.56 %) were obtained. The biodistribution of ¹²⁵I-Zaleplon and ¹²⁵I-Trazodone were studied in normal mice indicating the suitability of these labeled compounds to be used as radiopharmaceuticals for brain imaging. In addition, the labeling of Carbamazepine with Tc-99m was successfully done in this investigation. The optimum conditions required to give a radiochemical yield of 99% were 0.2 mg of CBZ, 50 µg of freshly prepared SnCl₂.2H₂Oand 200 µl phosphate buffer (ph 7) where the reaction mixture was heated at 50 degree C for 30 min. The biodistribution of ^99mTc-CBZ was studied in normal mice. The biodistribution of the tracer demonstrated the possibility of using this tracer as imaging agent for brain