Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Nucl Med. 2012 May;53(5):805-12. doi: 10.2967/jnumed.111.098186. Epub 2012 Apr 9.
Separate measurements of B(max), the density of available receptors, and K(D), the equilibrium dissociation constant in the human brain, with PET have contributed to our understanding of neuropsychiatric disorders, especially with respect to the dopamine D(2)/D(3) receptor system. However, existing methods have limited applications to the whole striatum, putamen, or caudate nucleus. Improved methods are required to examine B(max) and K(D) in detailed functional striatal subdivisions that are becoming widely used.
In response, a new method (bolus-plus-infusion transformation [BPIT]) was developed. After completion of a validation study for (11)C-raclopride scans involving 81 subjects, age-associated changes in B(max) and K(D) were examined in 47 healthy subjects ranging in age from 18 to 77 y.
The BPIT method was consistent with established reference tissue methods regarding regional binding potential. BPIT yielded time-consistent estimates of B(max) and K(D) when scan and infusion lengths were set equal in the analysis. In addition, BPIT was shown to be robust against PET measurement errors when compared with a widely accepted transient equilibrium method. Altogether, BPIT was supported as a method for regional binding potential, B(max), and K(D). We demonstrated age-associated declines in B(max) in all 5 functional striatal subdivisions with BPIT when corrected for multiple comparisons. These age-related effects were not consistently attainable with the transient equilibrium method. Irrespective to methods, K(D) remained unchanged with age.
The BPIT approach may be useful for understanding dopamine receptor abnormalities in neuropsychiatric disorders by enabling separate measurements of B(max) and K(D) in functional striatal subdivisions.
为了理解神经精神疾病，特别是多巴胺 D₂/ D₃受体系统，正电子发射断层扫描（PET）中已分别对 Bmax（受体密度）和 K D（平衡解离常数）进行了测量。然而，现有的方法在整个纹状体、壳核或尾状核的应用有限。需要改进方法来检查在详细的功能纹状体分区中 Bmax 和 K D 的应用，这些分区正在得到广泛应用。
为此，开发了一种新方法（bolus-plus-infusion transformation，BPIT）。在涉及 81 名受试者的（11）C-氯丙嗪扫描验证研究完成后，对 47 名年龄在 18 岁至 77 岁的健康受试者进行了 Bmax 和 K D 的年龄相关性变化检查。
BPIT 方法与区域结合势的既定参考组织方法一致。当在分析中设置扫描和输注长度相等时，BPIT 产生了时间一致的 Bmax 和 K D 估计值。此外，与广泛接受的瞬态平衡方法相比，BPIT 被证明对 PET 测量误差具有稳健性。总的来说，BPIT 支持作为区域结合势、Bmax 和 K D 的方法。我们用 BPIT 证明了在所有 5 个功能纹状体分区中，与年龄相关的 Bmax 下降，并且经过了多次比较的校正。这些与年龄相关的影响在瞬态平衡方法中并不总是能够达到。无论方法如何，K D 与年龄无关。
BPIT 方法可能通过在功能纹状体分区中分别测量 Bmax 和 K D，有助于理解神经精神疾病中的多巴胺受体异常。
