Preliminary Basic And Clinical Studies On Positron Emission Tomography: The Study On Positron Emitting Radipharmaceuticals

Over the past 10 years, advances in radiotracer chemistry and positron emission tomography (PET) instrumentation have merged to make PET a powerful scientific tool in the biomedical sciences. However, it is advances in positron emitting radiopharmaceticals that have played the pivotal role in driving the new directions in the studies of human physiology. Positron emitting radiopharmaceticals can't be imported because of its short half life. But, the study of 18F labeled molecular probes become increasingly attractive due to the relatively long half life of 18F (t1/2 is 109min) and can be used outside PET centers.Considerable evidence has estabolished in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system (CNS) closely related to patients with major depression. Among many neurotransmitters within serotonergic neuronal, 5-HT1A and serotonin transporter (SERT) are thought to be closely associated with the pathology of depression, unfortunately the trends and mechanisms of the variation of 5-HT1A and SERT are unclear. Not surprisingly much of this work has focused on the development of 18F labeled radiotracers for 5-HT system, particularly the 5-HT1A and SERT. Imaging with PET would be uttermost important value in elucidating mechanism of depression by acquiring living, functional, quantitative and objective imaging indexes. As we know that depression processes are driven by the complex interplay of several neurotransmitters and that their disruptions involved in CNS. Therefore we develop a 18F labeled 5-HT1A receptor imaging agent: 4-fluoro-N-[2- [1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pridinyl-benzamide(18F-MPPF), then to evaluate the binding characteristic of 18F-MPPF to 5-HT1A receptor, and also to investigate the binding potential of 5-HT1A receptor, SERT and dopamine transporter (DAT) on chronic unpredictable mild stress(CUMS) depressed rats.One of the major challenges before noninvasive myocardial imaging is the differentiation of viable, potentially functional tissue, and scarred myocardium with no potential or functional recovery. Viability assessments are most challenging in dysfunctional ventricular territories with prior ischemic damage. Noninvasive imaging modalities currently used to assess myocardial viability include PET imaging with18F-FDG and fatty acid. But the role of 18F-FDG PET imaging is quite limited by many factors. Morever, fatty acids have the potential to study myocardial metabolism and viability, and may be superior to conventional tracers for viability assessment. The clinical application of fatty acids in assessment of myocardial viability in our country is a blank due to lack of 123I. We develop 18F labeled fatty acid: 14(R,S)-fluoro-6-thia-hepat adecanoic acid(18F-FTHA) and β-methyl fluorophenyl pentadecanoic acid(18F-BMFPP) based upon our own structure-activity study, and evaluate both 18F-FTHA and 18F-BMFPP in rats and mice.Our study involves two parts. Part one: The experimental study on 18F labeled molecular probes in 5-HT system and their evaluations in CUMS depressed rats. Part two: The study on 18F labeled fatty acids myocardial imaging agents.Part one1,The preparation of 5-HT1A receptor imaging agent: 18F-MPPFLabeling precursor MPPNO2 and non-radioactive MPPF were synthesized. Nucleophilic substitution of fluoro replacement reaction was proceeded by oil-bath heating and microwave heating. Radiochemical yield of microwave heating (34~50%) was higher than oil-bath heating(8~24%),and the total synthetic time of microwave heating(40~50min) was also shorter than oil-heating(70~90min). Radiochemical purity(RCP) determined by thin layer chromatography(TLC) and high pressure liquid chromatography(HPLC) are both over 95%. The retention time(tR) of 18F-, 18F-MPPF and MPPNO2 are 2.80min, 8.25min, and 16.43min, respectively. 18F-MPPF was stable at room temperature for 3 hours. Partition coefficient(PC) were 1.46 and 1.72 at pH7.00 and pH7.40, respectively. The optimal condit...