PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.
PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.
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发表时间：
2000-02
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通讯作者：
C. V. van Dyck;P. Tan;R. Baldwin;L. Amici;P. Garg;C. Ng;R. Soufer;D. Charney;R. Innis
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作者：
C. V. van Dyck;P. Tan;R. Baldwin;L. Amici;P. Garg;C. Ng;R. Soufer;D. Charney;R. Innis
未标记的[18F]阿坦色林已被用于标记血清素5-HT 2A受体，其被认为在精神分裂症和抑郁症的病理生理学中是重要的。本研究的目的是测试恒定输注范例用于[18F]阿坦色林与PET的平衡建模的可行性。[18F]阿坦色林的动力学建模可能会受到静脉给药后血浆中观察到的亲脂性放射性代谢物的阻碍。方法8名健康志愿者在注射后555 - 626 min（615+/-24 min）内静脉注射[18F]阿坦色林（208+/-9 MBq [5.62+/-0.25 mCi]）加恒定输注（65+/-3 MBq/h [1.76+/-0.08 mCi/h]）。在整个输注期间，每30-60分钟进行一次PET采集（10-20分钟）和静脉采血。结果线性回归分析显示，脑活动和血浆[18 F]阿坦色林及其代谢物浓度的时间-活动曲线在约6 h后稳定。这允许平衡建模和估计V3'（6小时后特异性摄取[皮质-小脑]与总血浆母体浓度的比值）。V3'值的范围从前扣带皮层的1.57+/-0.38到额叶皮层的1.02+/-0.39。还计算了结合电位V3（6 h后特异性摄取与游离血浆母体浓度的比值，使用组平均值f1），范围为前扣带回皮质169+/-41至额叶皮质110+/-42。从6小时开始，V3'和V3的变化率仅为1.11+/-1.69%/h。结论这些结果证明了[18 F]阿坦色林在超过5个放射性半衰期内平衡成像的可行性，并提出了一种克服与亲脂性放射性标记代谢物相关的困难的方法。一旦达到平衡，V3和V3'的稳定性表明在6小时获得的单次PET采集可以提供5-HT 2A受体密度的合理测量。
UNLABELLED [18F]altanserin has been used to label serotonin 5-HT2A receptors, which are believed to be important in the pathophysiology of schizophrenia and depression. The purpose of this study was to test the feasibility of a constant infusion paradigm for equilibrium modeling of [18F]altanserin with PET. Kinetic modeling with [18F]altanserin may be hampered by the presence of lipophilic radiometabolites observed in plasma after intravenous administration. METHODS Eight healthy volunteers were injected with [18F]altanserin as a bolus (208+/-9 MBq [5.62+/-0.25 mCi]) plus constant infusion (65+/-3 MBq/h [1.76+/-0.08 mCi/h]) ranging from 555 to 626 min (615+/-24 min) after injection. PET acquisitions (10-20 min) and venous blood sampling were performed every 30-60 min throughout the infusion period. RESULTS Linear regression analysis revealed that time-activity curves for both brain activity and plasma [18F]altanserin and metabolite concentrations stabilized after about 6 h. This permitted equilibrium modeling and estimation of V3' (ratio of specific uptake [cortical-cerebellar] to total plasma parent concentration after 6 h). Values of V3' ranged from 1.57+/-0.38 for anterior cingulate cortex to 1.02+/-0.39 for frontal cortex. The binding potential V3 (ratio of specific uptake to free plasma parent concentration after 6 h, using group mean f1) was also calculated and ranged from 169+/-41 for anterior cingulate cortex to 110+/-42 for frontal cortex. From 6 h onward, the rate of change for V3' and V3 was only 1.11+/-1.69 %/h. CONCLUSION These results demonstrate the feasibility of equilibrium imaging with [18F]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled metabolites. The stability in V3 and V3' once equilibrium is achieved suggests that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT2A receptor density.