Malison R T, Vessotskie J M, Kung M P, McElgin W, Romaniello G, Kim H J, Goodman M M, Kung H F
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
J Nucl Med. 1995 Dec;36(12):2290-7.
The regional distribution, kinetics and pharmacological specificity of a new radioiodinated cocaine analog, N-((E)-3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl) tropane ([123I]IPT) were examined in brain SPECT studies (n = 20) of nonhuman primates.
Radiolabeling and purification of the iododestannylated trialkyltin percursor yielded the tracer at greater than 90% radiochemical purity and high (> 20,000 Ci/mmole) specific activity. Cynomologous monkeys were injected with 7.2 +/- 1.3 mCi (mean +/- s.d.) of the tracer, and serial 10-min images were acquired (total scan time = 177 +/- 22 min). Images were reconstructed as transaxial slices (2 mm) using restorative techniques (Wiener prefiltering).
Radioactivity concentrated quickly in striatal regions (time of peak = 25 +/- 13 min) and cleared gradually thereafter (8.8 +/- 4.6% hr). Striatal-to-cerebellar ratios of 2.6 +/- 1.5 (n = 19), 6.7 +/- 3.2 (n = 20), 15.1 +/- 10.7 (n = 10) and 22.8 +/- 11.0 (n = 9) were observed at the time of peak and at 1, 2 and 3 hr p.i., respectively. In contrast, extrastriatal activity peaked earlier and at lower levels, cleared more rapidly and resembled cerebellar time-activity curves. Displacing doses of nonspecific antagonists of monoamine transporters (mazindol and beta-CIT) showed that 95% of specific [123I]IPT binding was reversible, while selective antagonists (e.g., paroxetine, nisoxetine and GBR 12909) demonstrated that striatal activity was specifically associated with dopamine transporters.
These results indicate that [123I]IPT is a useful radioligand for in vivo SPECT imaging of striatal dopamine transporters.
在对非人类灵长类动物进行的脑单光子发射计算机断层扫描（SPECT）研究（n = 20）中，检测了一种新的放射性碘化可卡因类似物N-((E)-3-碘代丙烯-2-基)-2β-甲氧羰基-3β-(4-氯苯基)托烷（[123I]IPT）的区域分布、动力学和药理学特异性。
对碘脱锡三烷基锡前体进行放射性标记和纯化，得到放射化学纯度大于90%且比活度高（> 20,000 Ci/mmol）的示踪剂。给食蟹猴注射7.2±1.3 mCi（平均值±标准差）的示踪剂，并采集连续10分钟的图像（总扫描时间 = 177±22分钟）。使用恢复技术（维纳预滤波）将图像重建为横断面切片（2毫米）。
放射性迅速集中在纹状体区域（峰值时间 = 25±13分钟），此后逐渐清除（每小时8.8±4.6%）。在峰值时以及注射后1、2和3小时，纹状体与小脑的比值分别为2.6±1.5（n = 19）、6.7±3.2（n = 20）、15.1±10.7（n = 10）和22.8±11.0（n = 9）。相比之下，纹状体以外的活性峰值出现得更早且水平更低，清除得更快，并且类似于小脑的时间-活性曲线。单胺转运体非特异性拮抗剂（吗茚酮和β-CIT）的置换剂量表明，95%的特异性[123I]IPT结合是可逆的，而选择性拮抗剂（如帕罗西汀、尼索西汀和GBR 12909）表明纹状体活性与多巴胺转运体特异性相关。
这些结果表明，[123I]IPT是用于纹状体多巴胺转运体体内SPECT成像的有用放射性配体。
