Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Mol Imaging Biol. 2011 Aug;13(4):737-46. doi: 10.1007/s11307-010-0380-3.
Using positron emission tomography in isoflurane-anaesthetised cat, we recently demonstrated that the effect of D-amphetamine (AMPH) was greater on the binding potential (BP(ND)) of the agonist dopamine D2/D3 radiotracer (+)-4-[(11)C]propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1, 4]oxazin-9-ol ([(11)C]-(+)-PHNO) than on that of the antagonist [(11)C]-raclopride, a finding that we were unable to replicate in conscious rat. Herein we tested whether isoflurane differentially affects the AMPH sensitivity of [(11)C]-(+)-PHNO and [(3)H]-raclopride.
Conscious or isoflurane-anaesthetised rats pretreated intravenously (i.v.) with saline or 4 mg/kg AMPH were co-injected i.v. with [(11)C]-(+)-PHNO/[(3)H]-raclopride or [(3)H]-(+)-PHNO/[(11)C]-(-)-N-propyl-norapomorphine ([(11)C]-(-)-NPA) and euthanised 2, 10, 20, 30, 40 or 60 min following [(11)C]-(+)-PHNO/[(3)H]-raclopride or 60 min following [(3)H]-(+)-PHNO/[(11)C]-(-)-NPA. Striatal binding at 60 min, estimated by the specific binding ratio (SBR) and the binding potential with respect to non-displaceable binding (BP(ND)) for pseudodynamic data, was calculated using the simplified reference tissue model.
Isoflurane increased [(11)C]-(+)-PHNO, [(3)H]-(+)-PHNO and [(11)C]-(-)-NPA SBR (mean ± SD) by 80 ± 30%, 170 ± 50% and 120 ± 40%, and doubled the effect of AMPH on the SBR of these radiotracers to -61 ± 9%, -69 ± 12% and -60 ± 12%, respectively. Neither effect was seen for [(3)H]-raclopride SBR. Similar results were observed for [(11)C]-(+)-PHNO and [(3)H]-raclopride BP(ND).
Isoflurane differentially increases the binding and AMPH sensitivity of [(11)C]-(+)-PHNO and [(11)C]-(-)-NPA relative to [(3)H]-raclopride, suggesting that agonist radiotracers will prove no more effective for imaging dopaminergic activity in human than antagonist radiotracers.
我们最近使用正电子发射断层扫描技术在异氟烷麻醉的猫中证明，D-苯丙胺（AMPH）对激动剂多巴胺 D2/D3 放射性示踪剂[（11）C] - 4 - [（11）C]丙基-3,4,4a,5,6,10b-六氢-2H-萘并[1,2-b] [1,4]恶嗪-9-醇（[（11）C] - （+）-PHNO）结合潜力（BP（ND）的影响大于拮抗剂[（11）C] - 拉莫三嗪，我们无法在清醒大鼠中复制这一发现。在此，我们测试了异氟烷是否会使[（11）C] - （+）-PHNO和[（3）H] - 拉莫三嗪的 AMPH 敏感性产生差异。
静脉（i.v.）预静脉注射盐水或 4mg/kg AMPH 的清醒或异氟烷麻醉大鼠与[（11）C] - （+）-PHNO / [（3）H] - 拉莫三嗪或[（3）H] - （+） - PHNO / [（11）C] - （-）-N-丙基-norapomorphine（[（11）C] - （-）-NPA）共同静脉内注射，并在[（11）C] - （+） - PHNO / [（3）H] - 拉莫三嗪后 2、10、20、30、40 或 60 分钟或[（3）H] - （+） - PHNO / [（11）C] - （-）-NPA 后 60 分钟处死。通过简化参考组织模型，使用伪动态数据的特异性结合比（SBR）和相对于不可置换结合的结合潜力（BP（ND））来计算 60 分钟时纹状体的结合，以进行估算。
异氟烷使[（11）C] - （+） - PHNO，[（3）H] - （+） - PHNO 和[（11）C] - （-）-NPA 的 SBR（平均值±标准差）分别增加了 80±30％，170±50％和 120±40％，并将 AMPH 对这些示踪剂 SBR 的作用增加了一倍，分别为-61±9％，-69±12％和-60±12％。[（3）H] - 拉莫三嗪的 SBR 没有观察到这种效果。[（11）C] - （+） - PHNO 和[（3）H] - 拉莫三嗪的 BP（ND）也得到了类似的结果。
异氟烷使[（11）C] - （+） - PHNO 和[（11）C] - （-）-NPA 的结合和 AMPH 敏感性相对于[（3）H] - 拉莫三嗪增加，这表明与拮抗剂放射性示踪剂相比，激动剂放射性示踪剂对人类多巴胺能活性的成像效果不会更好。
