Fischman A J, Bonab A A, Babich J W, Palmer E P, Alpert N M, Elmaleh D R, Callahan R J, Barrow S A, Graham W, Meltzer P C, Hanson R N, Madras B K
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Synapse. 1998 Jun;29(2):128-41. doi: 10.1002/(SICI)1098-2396(199806)29:2<128::AID-SYN4>3.0.CO;2-9.
Increasing evidence indicates that dopamine (DA) transporter density declines in Parkinson's disease (PD). 2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop-1-en -3-yl) nortropane (IACFT, Altropane) is a cocaine analog with high affinity and selectivity for dopamine transporter (DAT) sites in the striatum. In this study, single photon emission computed tomography (SPECT) with [123I]altropane was used to measure DAT density in seven healthy volunteers (five males, age 37-75, and two females, ages 26 and 39) and eight male patients with Parkinson's disease (age 14-79, Hoehn and Yahr stage: 1.5-3 (n = 5) and 4-5 (n = 3)). Dynamic SPECT images and arterial blood samples were acquired over 1.5-2 hr and plasma radioactivity was analyzed chromatographically to obtain metabolite corrected arterial input functions. Binding potential (BP, B'max/KD) for striatal (Str) DAT sites was calculated by two methods using occipital cortex (Occ) as a reference. In the first method, tissue time-activity curves (TAC) and metabolite corrected arterial input functions were analyzed by a linear graphical method developed for reversible receptor ligands. In the second method, the expression (Str(TAC) - Occ(TAC)) was fitted to a gamma variate function and the maximum divided by Occ(TAC) at the same time was used to estimate BP. In five of the PD patients, the SPECT data were compared with the results of PET with [18F] 6-fluoro DOPA (FD-PET). Plasma analysis indicated that [123I]altropane is rapidly converted to polar metabolites. SPECT images in healthy volunteers showed that [123I] altropane accumulated rapidly and selectively in the striatum and yielded excellent quality images within 1 h after injection. Both methods of analysis revealed a 7.6%/decade reduction in BP and average striatal values (corrected to age 25) were 1.83 +/- 0.22 and 2.09 +/- 0.20 by methods 1 and 2. In all the PD patients, striatal accumulation was markedly reduced and the pattern of loss was similar to that reported for DA; most profound in the posterior putamen with relative sparing of the caudate nuclei. A comparable pattern was observed with FD-PET. For total striatum, age-corrected BP was significantly (P < 0.001) reduced; 0.83 +/- 0.06 (method 1), 0.84 +/- 0.07 (method 2). BPs measured by the two methods were remarkably similar and highly correlated r2 = 0.88, (P < 0.001). These results indicate that [123I]altropane is an excellent SPECT ligand for imaging the DAT/DA neurons in human brain. The high selectivity and rapid striatal accumulation of the ligand allows for accurate quantitation of DAT sites in less than 2 hr. The results further demonstrate that [123I]altropane is an effective marker for PD.
越来越多的证据表明，帕金森病（PD）中多巴胺（DA）转运体密度下降。2β-甲氧羰基-3β-（4-氟苯基）-N-（1-碘丙-1-烯-3-基）去甲托烷（IACFT，阿曲库铵）是一种可卡因类似物，对纹状体中的多巴胺转运体（DAT）位点具有高亲和力和选择性。在本研究中，使用[123I]阿曲库铵单光子发射计算机断层扫描（SPECT）测量了7名健康志愿者（5名男性，年龄37 - 75岁，2名女性，年龄26岁和39岁）和8名男性帕金森病患者（年龄14 - 79岁，Hoehn和Yahr分期：1.5 - 3期（n = 5）和4 - 5期（n = 3））的DAT密度。在1.5 - 2小时内采集动态SPECT图像和动脉血样，并通过色谱法分析血浆放射性以获得代谢物校正的动脉输入函数。以枕叶皮质（Occ）为参考，通过两种方法计算纹状体（Str）DAT位点的结合潜能（BP，B'max/KD）。在第一种方法中，通过为可逆受体配体开发的线性图形方法分析组织时间 - 活性曲线（TAC）和代谢物校正的动脉输入函数。在第二种方法中，将表达式（Str（TAC） - Occ（TAC））拟合为伽马变异函数，并将最大值除以同一时间的Occ（TAC）来估计BP。在5名PD患者中，将SPECT数据与[18F] 6 - 氟多巴（FD - PET）的PET结果进行了比较。血浆分析表明，[123I]阿曲库铵迅速转化为极性代谢物。健康志愿者的SPECT图像显示，[123I]阿曲库铵在纹状体中迅速且选择性地积聚，并在注射后1小时内产生高质量图像。两种分析方法均显示BP每十年降低7.6％，方法1和方法2校正至25岁后的平均纹状体值分别为1.83±0.22和2.09±0.20。在所有PD患者中，纹状体积聚明显减少，损失模式与DA报道的相似；在后部壳核中最明显，尾状核相对保留。FD - PET观察到类似的模式。对于整个纹状体，年龄校正后的BP显著降低（P < 0.001）；0.83±0.06（方法1），0.84±0.07（方法2）。两种方法测量的BP非常相似且高度相关，r2 = 0.88，（P < 0.001）。这些结果表明，[123I]阿曲库铵是用于成像人脑中DAT/DA神经元的优秀SPECT配体。该配体的高选择性和纹状体快速积聚允许在不到2小时内准确定量DAT位点。结果进一步证明，[123I]阿曲库铵是PD的有效标志物。
