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在 6-OHDA 损伤大鼠中测量多巴胺能功能:PET 和微透析的比较。

Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET and microdialysis.

机构信息

Department of Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, British Columbia V6T 1Z1, Canada.

出版信息

EJNMMI Res. 2013 Oct 2;3(1):69. doi: 10.1186/2191-219X-3-69.

DOI:10.1186/2191-219X-3-69
PMID:24088510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3875899/
Abstract

BACKGROUND

[18 F]fluorodopa (FDOPA) positron emission tomography (PET) allows assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's disease. We examined how [18 F]FDOPA PET-derived kinetic parameters relate the dopamine (DA) and DA metabolite content of extracellular fluid measured by microdialysis to aid in the interpretation of data from both techniques.

METHODS

[18 F]FDOPA PET imaging and microdialysis measurements were performed in unilaterally 6-hydroxydopamine-lesioned rats (n = 8) and normal control rats (n = 3). Microdialysis testing included baseline measurements and measurements following acute administration of LDOPA. PET imaging was also performed using [11C]dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine transporter marker and allowed assessment of denervation severity.

RESULTS

The different methods provided highly correlated data. Lesioned rats had reduced DA metabolite concentrations ipsilateral to the lesion (p < 0.05 compared to controls), with the concentration being correlated with FDOPA's effective distribution volume ratio (EDVR; r = 0.86, p < 0.01) and DTBZ's binding potential (BPND; r = 0.89, p < 0.01). The DA metabolite concentration in the contralateral striatum of severely (>80%) lesioned rats was lower (p < 0.05) than that of less severely lesioned rats (<80%) and was correlated with the ipsilateral PET measures (r = 0.89, p < 0.01 for BPND) but not with the contralateral PET measures. EDVR and BPND in the contralateral striatum were not different from controls and were not correlated with the denervation severity.

CONCLUSIONS

The demonstrated strong correlations between the PET and microdialysis measures can aid in the interpretation of [18 F]FDOPA-derived kinetic parameters and help compare results from different studies. The contralateral striatum was affected by the lesioning and so cannot always serve as an unaffected control.

摘要

背景

[18F]氟多巴(FDOPA)正电子发射断层扫描(PET)允许评估左旋多巴(LDOPA)的代谢,并且广泛用于研究帕金森病。我们研究了[18F]FDOPA PET 衍生的动力学参数与通过微透析测量的细胞外液中多巴胺(DA)和 DA 代谢物含量的关系,以帮助解释两种技术的数据。

方法

在单侧 6-羟多巴胺损伤大鼠(n=8)和正常对照大鼠(n=3)中进行[18F]FDOPA PET 成像和微透析测量。微透析测试包括基线测量和 LDOPA 急性给药后的测量。PET 成像也使用[11C]二氢四苯并嗪(DTBZ)进行,DTBZ 是囊泡单胺转运体标志物的配体,允许评估去神经支配的严重程度。

结果

不同的方法提供了高度相关的数据。损伤大鼠损伤侧的 DA 代谢物浓度降低(与对照组相比,p < 0.05),浓度与 FDOPA 的有效分布容积比(EDVR;r = 0.86,p < 0.01)和 DTBZ 的结合潜能(BPND;r = 0.89,p < 0.01)相关。严重(>80%)损伤大鼠对侧纹状体的 DA 代谢物浓度较低(p < 0.05),与同侧 PET 测量值相关(r = 0.89,p < 0.01 用于 BPND),但与对侧 PET 测量值不相关。对侧纹状体的 EDVR 和 BPND 与对照组无差异,与去神经支配的严重程度无关。

结论

所证明的 PET 和微透析测量之间的强相关性可以帮助解释[18F]FDOPA 衍生的动力学参数,并有助于比较不同研究的结果。损伤对侧纹状体受到损伤的影响,因此不能始终作为未受影响的对照。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/8ad66c3f95f2/2191-219X-3-69-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/8245a9656153/2191-219X-3-69-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/ae9f581bc370/2191-219X-3-69-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/eb6f6265d0ef/2191-219X-3-69-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/41e40fa9c482/2191-219X-3-69-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/0437d6a11599/2191-219X-3-69-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/8ad66c3f95f2/2191-219X-3-69-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/8245a9656153/2191-219X-3-69-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/ae9f581bc370/2191-219X-3-69-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/eb6f6265d0ef/2191-219X-3-69-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/41e40fa9c482/2191-219X-3-69-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/0437d6a11599/2191-219X-3-69-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e3c/3875899/8ad66c3f95f2/2191-219X-3-69-6.jpg

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