Kinetic Analysis of [11C]Vorozole Binding in the Human Brain with Positron Emission Tomography
Kinetic Analysis of [11C]Vorozole Binding in the Human Brain with Positron Emission Tomography
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DOI：
10.2310/7290.2014.00004
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发表时间：
2014-05-01
影响因子：
2.8
通讯作者：
Biegon, Anat
中科院分区：
文献类型：
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作者：
Logan, Jean;Kim, Sung Won;Biegon, Anat
使用正电子发射断层扫描，我们研究了[C-11]伏罗唑（[C-11]VOR）的动力学，[C-11] VOR是催化雌激素生物合成最后一步的芳香酶的放射性示踪剂。6名受试者在基线条件下进行扫描，2周后进行复检。重新测试后，用2.5 mg芳香酶抑制剂来曲唑进行阻断研究。使用基线和阻断的总组织分布体积（V-T）根据Lassen图估计结合潜力（BPNDA）。丘脑的BPNDA比小脑高15倍。从来曲唑的研究中，我们发现[C-11]VOR表现出一个缓慢的结合区室（小k（4）），具有非特异性和可阻断的成分。由于V-T对k（4）的变化敏感，因此对四个最高结合区域使用共同值。我们还考虑了60至90分钟的组织摄取与血浆比率作为结果测量。使用比率法，最高和最低之间的差异为2.4，而V-T为3.5。比值法低估了高区域，但变量较小，可能更适合患者研究。由于其动力学和分布，该示踪剂不是推注或参考组织方法的候选者。
Using positron emission tomography, we investigated the kinetics of [C-11]vorozole ([C-11]VOR), a radiotracer for the enzyme aromatase that catalyzes the last step in estrogen biosynthesis. Six subjects were scanned under baseline conditions followed by retest 2 weeks later. The retest was followed by a blocking study with 2.5 mg of the aromatase inhibitor letrozole. The binding potential (BPNDA) was estimated from a Lassen plot using the total tissue distribution volume (V-T) for baseline and blocked. BPNDA for the thalamus was found to be 15 times higher than that for the cerebellum. From the letrozole studies, we found that [C-11]VOR exhibits a slow binding compartment (small k(4)) that has a nonspecific and a blockable component. Because of the sensitivity of V-T to variations in k(4), a common value was used for the four highest binding regions. We also considered the tissue uptake to plasma ratio for 60 to 90 minutes as an outcome measure. Using the ratio method, the difference between the highest and lowest was 2.4 compared to 3.5 for the V-T. The ratio method underestimates the high regions but is less variable and may be more suitable for patient studies. Because of its kinetics and distribution, this tracer is not a candidate for a bolus infusion or reference tissue methods.