博士 / 國立陽明大學 / 生物醫學影像暨放射科學系暨研究所 / 98 / Alzheimer’s disease (AD) is one of the epidemic neurodegeneration disease-affecting millions in elders. In AD, much number of dystrophic neuritis has been shown to correlate with the clinical severity of dementia, and neuronal dystrophy is associated with synaptic loss in cortical cultures exposed to fibrillar A? (??amyloid). As senile plaques (SPs) and neurofibrillay tangles (NFTs) are hallmarks in AD. Histological dye analogs, like Thioflavin-S, had many kinds of biomarker for mapping A?? [18F]FDDNP (2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl} ethylidene)malononitrile) and [123I]IMPY (6-iodo-2-(4?S-dimethylamino)phenylimidazo [1,2-a]-pyridine), also showed the superiority characteristics in binding with SPs and NFTs. In the article, we modified the protocol on an auto-synthesizer and used these radiopharmaceuticals in vitro, in vivo and ex vivo study for identification.
In the first, modification of the protocol on an auto-synthesizer (by [18F]FDG and [123I]ADAM) and wish to use the high purity radiopharmaceuticals in the future study. In radio-synthesis, higher quality product by in-house-labeling [18F]FDDNP. (95%, identified by radioHPLC, yield about the 30%) and in [123I]IMPY (98%, identified by radioTLC, yield about the 30%). Identify the lipophilic by the partition coefficient test, and the result values were 1.93 and 1.82, respectively. It means higher lipophilic could had ability to penetrate the blood brain barrier (BBB).
Second, in in vitro assays by the competitive assay showed that [18F]FDDNP high selectivity and specificity in Tg2576 brain region (selectivity between hippocampus and frontal cortex were 2.10 ± 0.34 and 1.90 ± 0.17, respectively (compare with cerebellum), specificity between hippocampus and frontal cortex were 4.62 ± 1.58 and 7.27 ± 5.53, respectively (compare with cold FDDNP)). And in [123I]IMPY, hippocampus of transgenic mice compared with controls showed 2.04 ?b 0.37 times accumulated, while the frontal cortex showed 2.12 ?b 0.47 times. In addition of the competitive assay for the IMPY: the hippocampus of Tg2576 transgenic mice showed 1.16 ?b 0.34 times than controls while the cortical cortex in transgenic mice showed 1.22 ?b 0.40 times of controls.
Third, in ex vivo assay, [18F]FDDNP and [123I]IMPY in post-injected 30min in frontal cortex and hippocampus in transgenic mice compare to control mice had 4.39 and 2.19 folds (in frontal cortex) and 3.09 and 2.40 folds (in hippocampus), in FDDNP and IMPY.
Fourth, in in vivo assay, microPET or microSPECT showed that Tg2576 brain section/reference (cerebellum or muscle) ratio lager than control mice. In microPET the ratio was about 0.83 to 1.00 in Tg2576 mice compare with muscle, and in control mice the ratio between muscle only had 0.05 to 0.19 in different brain region (like cortex, stratum, thalamus, and cerebellum) by [18F]FDDNP. In microSPECT the Tg2576 mice had 2.8 and 2.9 fold between frontal cortex and thalamus to cerebellum, and in control group only had 1.5 and 1.4 fold by [123I]IMPY.
All of those results, synthesize of [18F]FDDNP and [123I]IMPY were success. Higher quality product and in those experiments were showed the superiority results. In vitro competitive assay and ex vivo assay showed that [18F]FDDNP and [123I]IMPY is available for tracing A? in AD research. In the past, researcher less the imaging report by transgenic mice. But in my in vivo imaging study had encourage result by this kind of radiopharmaceuticals, and wish to exploitative the preclinical platform for early diagnosis on AD patients.
| Identifer | oai:union.ndltd.org:TW/098YM005770025 |
| Date | January 2010 |
| Creators | Kang-Wei Chang, 張剛瑋 |
| Contributors | Hsin-Ell Wang, 王信二 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 102 |
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