| The main objectives of this dissertation are (a) to synthesize 99mTc labeled porphyrin-based compounds for non-invasive tumor diagnosis; (b) to design, synthesize and evaluate a series of 99mTc labeled ligands for D4 dopamine receptor imaging.; The employment of HPPH and its derivatives as vehicles to carry the N 2S2-99mTc complex to the target have successfully imaged the Ward colon tumor transplanted on the shoulder of F-344 rats in vivo. The biodistribution studies have demonstrated that the tumor uptake of [99mTc]HPPH-N2S2 complex is influenced by the time of postinjection and size of the tumor. The rat with the larger tumor size had a higher tumor uptake. The tumor uptake of the radioactivity increased with the time of postinjection, while the uptake at other organs, such as kidney, liver, lung and spleen decreased with the time. In addition, [99mTc]HPPH-2N2S2 and [99mTc]pyropheophorbide-a-N 2S2 complexes have shown the same level of tumor uptake, while their uptake at non-target tissues drops dramatically.; A series of Tc-99m labeled D4 receptor antagonists have been synthesized and evaluated as D4 receptor imaging agents, followed by the first structure-activity relationship (SAR) studies for the D4 receptor ligands. It was demonstrated that the incorporation of N2S2-99mTc complex to position 3 of the targeting molecules displayed the best binding affinity for D4 receptor. |
