Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, NY, 10032, USA.
Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
Mol Imaging Biol. 2018 Aug;20(4):667-681. doi: 10.1007/s11307-018-1165-3.
Inhibition of the isoform A of monoamine oxidase (MAO-A), a mitochondrial enzyme catalyzing deamination of monoamine neurotransmitters, is useful in treatment of depression and anxiety disorders. [C]harmine, a MAO-A PET radioligand, has been used to study mood disorders and antidepressant treatment. However, [C]harmine binding test-retest characteristics have to date only been partially investigated. Furthermore, since MAO-A is ubiquitously expressed, no reference region is available, thus requiring arterial blood sampling during PET scanning. Here, we investigate [C]harmine binding measurements test-retest properties; assess effects of using a minimally invasive input function estimation on binding quantification and repeatability; and explore binding potentials estimation using a reference region-free approach.
Quantification of [C]harmine distribution volume (V) via kinetic models and graphical analyses was compared based on absolute test-retest percent difference (TRPD), intraclass correlation coefficient (ICC), and identifiability. The optimal procedure was also used with a simultaneously estimated input function in place of the measured curve. Lastly, an approach for binding potentials quantification in absence of a reference region was evaluated.
[C]harmine V estimates quantified using arterial blood and kinetic modeling showed average absolute TRPD values of 7.7 to 15.6 %, and ICC values between 0.56 and 0.86, across brain regions. Using simultaneous estimation (SIME) of input function resulted in V estimates close to those obtained using arterial input function (r = 0.951, slope = 1.073, intercept = - 1.037), with numerically but not statistically higher test-retest difference (range 16.6 to 22.0 %), but with overall poor ICC values, between 0.30 and 0.57.
Prospective studies using [C]harmine are possible given its test-retest repeatability when binding is quantified using arterial blood. Results with SIME of input function show potential for simplifying data acquisition by replacing arterial catheterization with one arterial blood sample at 20 min post-injection. Estimation of [C]harmine binding potentials remains a challenge that warrants further investigation.
抑制单胺氧化酶 A（MAO-A）同工酶，一种催化单胺神经递质脱氨的线粒体酶，在治疗抑郁症和焦虑症方面很有用。[C]哈尔明是一种 MAO-A PET 放射性配体，已被用于研究情绪障碍和抗抑郁治疗。然而，[C]哈尔明结合测试-再测试特征迄今为止仅部分研究。此外，由于 MAO-A 广泛表达，因此没有参考区域，因此在 PET 扫描期间需要进行动脉采血。在这里，我们研究了[C]哈尔明结合测量的测试-再测试特性；评估使用微创输入函数估计对结合定量和可重复性的影响；并探索无参考区域的结合势估计方法。
通过动力学模型和图形分析比较了[C]哈尔明分布容积（V）的定量结果，基于绝对测试-再测试百分比差异（TRPD）、组内相关系数（ICC）和可识别性。还使用同时估计的输入函数代替测量曲线来优化程序。最后，评估了无参考区域时结合势定量的方法。
使用动脉血和动力学建模定量的[C]哈尔明 V 估计值在脑区之间的平均绝对 TRPD 值为 7.7%至 15.6%，ICC 值在 0.56 至 0.86 之间。使用输入函数的同时估计（SIME）得到的 V 估计值接近使用动脉输入函数（r=0.951，斜率=1.073，截距=-1.037）得到的估计值，但测试-再测试差异数值上但统计学上更高（范围 16.6 至 22.0%），但总体 ICC 值较差，在 0.30 至 0.57 之间。
考虑到使用动脉血定量时结合的测试-再测试重复性，使用[C]哈尔明进行前瞻性研究是可行的。使用输入函数 SIME 的结果表明，通过在注射后 20 分钟用一次动脉血样代替动脉导管插入术，可以简化数据采集。[C]哈尔明结合势的估计仍然是一个挑战，需要进一步研究。
