Rapid detection of Parkinson's disease by SPECT with altropane: A selective ligand for dopamine transporters
Rapid detection of Parkinson's disease by SPECT with altropane: A selective ligand for dopamine transporters
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使用阿托烷进行 SPECT 快速检测帕金森病：多巴胺转运蛋白的选择性配体
作者：
A. Fischman;A. Bonab;J. Babich;E. P. Palmer;N. Alpert;D. Elmaleh;R. Callahan;S. Barrow;W. Graham;P. Meltzer;R. Hanson;B. Madras
越来越多的证据表明，多巴胺（DA）转运体密度在帕金森病（PD）中下降。2β‐碳甲氧基‐3β‐（4‐氟苯基）‐n‐（1‐碘丙基‐1‐en‐3基）诺tropane （IACFT, Altropane™）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]altropane的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和39岁）和8名男性帕金森病患者（14-79岁，Hoehn和Yahr分期：1.5-3 （n = 5）和4-5 (n = 3)）的DAT密度。在1.5-2小时内获取动态SPECT图像和动脉血液样本，并用色谱分析血浆放射性以获得代谢物校正的动脉输入功能。以枕皮质（Occ）为参照，用两种方法计算纹状体（Str） DAT位点的结合电位（BP, B 'max /KD）。在第一种方法中，组织时间-活性曲线（TAC）和代谢物校正的动脉输入函数通过可逆受体配体开发的线性图形方法进行分析。在第二种方法中，将表达式（StrTAC−OccTAC）拟合到一个伽马变量函数中，同时使用最大值除以OccTAC来估计BP。在5例PD患者中，将SPECT数据与PET与[18F] 6‐氟多巴（FD‐PET）的结果进行比较。血浆分析表明[123I]阿曲烷能迅速转化为极性代谢物。健康志愿者的SPECT图像显示，[123I]阿曲烷在注射后1小时内迅速、选择性地在纹状体中积累，并产生了高质量的图像。两种分析方法均显示血压每十年降低7.6%，方法1和方法2的纹状体平均值（校正至25岁）分别为1.83±0.22和2.09±0.20。在所有PD患者中，纹状体积累明显减少，其损失模式与DA相似；在壳核后部最深，尾状核相对较少。FD‐PET观察到类似的模式。对于总纹状体，年龄校正后的血压显著（P < 0.001）降低；0.83±0.06（方法1），0.84±0.07（方法2）。两种方法测得的bp非常相似且高度相关，r2 = 0.88, （P < 0.001）。这些结果表明[123I]altropane是一种很好的成像人脑DAT/DA神经元的SPECT配体。配体的高选择性和快速纹状体积累允许在不到2小时内准确定量DAT位点。结果进一步证明[123I]阿曲烷是PD的有效标志物。突触29:28 - 141,1998。©1998 Wiley‐Liss, Inc。
Increasing evidence indicates that dopamine (DA) transporter density declines in Parkinson's disease (PD). 2β‐Carbomethoxy‐3β‐(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 (StrTAC − OccTAC) was fitted to a gamma variate function and the maximum divided by OccTAC 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. Synapse 29:128–141, 1998. © 1998 Wiley‐Liss, Inc.
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DOI：
10.1016/0883-2889(90)90191-i
发表时间：
1990
期刊：
International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes
影响因子：
--
作者：
Luxen,A;Perlmutter,M;Bida,GT;VanMoffaert,G;Cook,JS;Satyamurthy,N;Phelps,ME;Barrio,JR
通讯作者：
Barrio,JR
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DOI：
--
发表时间：
1997
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Fischman,AJ;Babich,JW;Elmaleh,DR;Barrow,SA;Meltzer,P;Hanson,RN;Madras,BK
通讯作者：
Madras,BK
影响因子：
7.3
作者：
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通讯作者：
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影响因子：
3.6
作者：
Madras,BK;Spealman,RD;Fahey,MA;Neumeyer,JL;Saha,JK;Milius,RA
通讯作者：
Milius,RA
[123I]-2 beta-甲甲氧基-3 beta-(4-碘苯基)托烷：大脑中单胺再摄取位点的高亲和力 SPECT 放射性示踪剂。
影响因子：
7.3
作者：
Neumeyer,JL;Wang,SY;Milius,RA;Baldwin,RM;Zea-Ponce,Y;Hoffer,PB;Sybirska,E;al-Tikriti,M;Charney,DS;Malison,RT
通讯作者：
Malison,RT