Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY 10032, USA.
Neuroimage. 2012 Jan 2;59(1):271-85. doi: 10.1016/j.neuroimage.2011.07.001. Epub 2011 Jul 18.
Scanning properties and analytic methodology of the 5-HT2A receptor-selective positron emission tomography (PET) tracer 11C-MDL100907 have been partially characterised in previous reports. We present an extended characterisation in healthy human subjects.
64 11C-MDL100907 PET scans with metabolite-corrected arterial input function were performed in 39 healthy adults (18-55 years). 12 subjects were scanned twice (duration 150 min) to provide data on plasma analysis, model order estimation, and stability and test-retest characteristics of outcome measures. All other scans were 90 min duration. 3 subjects completed scanning at baseline and following 5-HT2A receptor antagonist medication (risperidone or ciproheptadine) to provide definitive data on the suitability of the cerebellum as reference region. 10 subjects were scanned under reduced 5-HT and control conditions using rapid tryptophan depletion to investigate vulnerability to competition with endogenous 5-HT. 13 subjects were scanned as controls in clinical protocols. Pooled data were used to analyse the relationship between tracer injected mass and receptor occupancy, and age-related decline in 5-HT2A receptors.
Optimum analytic method was a 2-tissue compartment model with arterial input function. However, basis function implementation of SRTM may be suitable for measuring between-group differences non-invasively and warrants further investigation. Scan duration of 90 min achieved stable outcome measures in all cortical regions except orbitofrontal which required 120 min. Binding potential (BPP and BPND) test-retest variability was very good (7-11%) in neocortical regions other than orbitofrontal, and moderately good (14-20%) in orbitofrontal cortex and medial temporal lobe. Saturation occupancy of 5-HT2A receptors by risperidone validates the use of the cerebellum as a region devoid of specific binding for the purposes of PET. We advocate a mass limit of 4.6 μg to remain below 5% receptor occupancy. 11C-MDL100907 specific binding is not vulnerable to competition with endogenous 5-HT in humans. Paradoxical decreases in BPND were found in right prefrontal cortex following reduced 5-HT, possibly representing receptor internalisation. Mean age-related decline in brain 5-HT2A receptors was 14.0±5.0% per decade, and higher in prefrontal regions.
Our data confirm and extend support for 11C-MDL100907 as a PET tracer with very favourable properties for quantifying 5-HT2A receptors in the human brain.
先前的报告已经部分描述了 5-羟色胺 2A 受体选择性正电子发射断层扫描（PET）示踪剂 11C-MDL100907 的扫描特性和分析方法。我们在健康的人类受试者中进行了更广泛的特征描述。
39 名健康成年人（18-55 岁）进行了 64 次 11C-MDL100907 PET 扫描，采用校正代谢物的动脉输入函数。12 名受试者进行了两次扫描（持续时间 150 分钟），以提供有关血浆分析、模型阶估计以及结果测量的稳定性和测试-重测特征的数据。所有其他扫描持续 90 分钟。3 名受试者在基线和 5-羟色胺 2A 受体拮抗剂（利培酮或赛庚啶）治疗后完成扫描，以提供小脑作为参考区域的适用性的明确数据。10 名受试者在使用快速色氨酸耗竭的情况下进行了减少 5-羟色胺和对照条件下的扫描，以研究与内源性 5-羟色胺竞争的易感性。13 名受试者在临床方案中作为对照进行扫描。汇总数据用于分析示踪剂注射质量与受体占有率以及与年龄相关的 5-羟色胺 2A 受体下降之间的关系。
最佳分析方法是具有动脉输入函数的 2 组织隔室模型。然而，SRTM 的基函数实现可能适合于无创测量组间差异，值得进一步研究。在除眶额皮质外的所有皮质区域，90 分钟的扫描持续时间可实现稳定的结果测量，而眶额皮质需要 120 分钟。除眶额皮质外，新皮质区域的结合潜力（BPP 和 BPND）测试-重测变异性非常好（7-11%），而眶额皮质和内侧颞叶的变异性则适度良好（14-20%）。利培酮对 5-羟色胺 2A 受体的饱和占有率验证了小脑作为缺乏特异性结合的区域的用途，适用于 PET。我们提倡将质量限制在 4.6 μg 以下，以保持低于 5%的受体占有率。在人类中，11C-MDL100907 的特异性结合不受内源性 5-羟色胺竞争的影响。在减少 5-羟色胺后，右侧前额叶皮质发现了 BPND 的反常下降，可能代表受体内化。大脑 5-羟色胺 2A 受体的年龄相关下降平均为每十年 14.0±5.0%，前额叶区域更高。
我们的数据证实并扩展了对 11C-MDL100907 的支持，它是一种具有非常有利特性的 PET 示踪剂，可用于定量人类大脑中的 5-羟色胺 2A 受体。
