Radionuclide production is always the first step of radiopharmaceutical research. The production of n.c.a.197Hg together with the short-lived 197mHg isomer is possible by proton or deuteron irradiation of natural gold using a cyclotron, as two promising nuclear reactions reported: 197Au(p,n)197(m)Hg reaction, 197Au(d,2n)197(m)Hg reaction. The access to n.c.a. 197(m)Hg should be in sufficient quantity and quality so as to be suitable for analytical studies and labeling studies with small scale and for animal and other preclinical studies on large scale. Moreover, an improved design by studying irradiation time and energy will provide the facility with sufficient quantity and quality for imaging and experimental therapeutically purposes. The development of a rapid, reliable method for Hg/Au separation represents an important prerequisite for increasing yields which will obtain 197(m)Hg in higher activity level with the product elution into a small volume. Here, many of previously established methods for mercury separation should be employed, such as distillation of the metal, extraction by organic solvents, extraction by resin, etc. However, owing to the different mechanisms, these separations do not always give satisfactory results. The purity and the final volume of product, efficiency, automatization and total processing time of separation procedure, these factors are extremely important for the next coming labeling studies. Therefore, comparison studies need to be employed to select the most suitable method enable for labeling studies. Establishing strategies for development of 197(m)Hg labeled in vivo stable labeling units. Several ready-to-use chelators are urgent needed before 197(m)Hg labeling unit conjugated with any specific targeted molecules. Numerous factors need to be considered for the development of the agents: Firstly, a robust synthetic and labeling strategy should be developed for the chelators or precursors of 197(m)Hg. Secondly, it should be strongly stable (especially bio-stability) to avoid the accumulation of radioactive substances in non-target organs. Thirdly, water solubility should be high enough for animal administration and avoid the toxicity of organic solvent. Fourthly, high selectivity (specificity) to avoid the transchelation/side reaction(s) with other metal ions. There are mainly two different approaches for 197(m)Hg labeling, first kind of ligands are based on Hg-S bonds, which form 197(m)Hg-S based compounds. It is well known that mercury shows strong ability on chelating of thiols, dithiols, disulfide, sulfur based and other sulfur rich interacting ligands, which shows great potentials for 197(m)Hg labeling. Thus, thiol based chelators should be investigated in the thesis. 197(m)Hg-organometallics was the second. Mercury is unique among metals in its capability to form covalent Hg-C bonds and has its own organic chemistry because the existence of large numbers of organic Hg compounds, which shows great potential to be labeled and applied in the field of radiopharmacy. After synthesizing novel agents, its theranostics capability should be accessed by a series of in vitro and in vivo studies. Depending on the type of different agents, the radiolabeling strategies should be optimized. Soon afterwards, detailed analytical and in vitro characterization with high-performance liquid chromatography (HPLC), radio thin-layer chromatography (radio-TLC), among other methods should be performed to determine several radiochemical behaviors such as labeling efficiency and stability. Besides, for the purpose of in vivo animal studies, removal of organic solvents and well-suited methods for purification of the radiolabeled units should be developed if necessary. Then, the most promising radiolabeled compounds were selected for further pharmacokinetic studies in rats. In vivo SPECT imaging studies should be employed for further investigations of radiopharmacological behaviors.