作为间碘苄胍替代物的潜在及实用的肾上腺髓质PET放射性药物：间-(ω-[¹⁸F]氟代烷基)苄胍

Potential and practical adrenomedullary PET radiopharmaceuticals as an alternative to m-iodobenzylguanidine: m-(omega-[18F]fluoroalkyl)benzylguanidines.

作者信息

Lee Byung Chul, Paik Jin-Young, Chi Dae Yoon, Lee Kyung-Han, Choe Yearn Seong

机构信息

Department of Chemistry, Inha University, 253 Yonghyundong Namgu, Inchon 402-751, Korea.

出版信息

Bioconjug Chem. 2004 Jan-Feb;15(1):104-11. doi: 10.1021/bc034115e.

DOI:10.1021/bc034115e

PMID:14733589

Abstract

To investigate adrenomedullary radiopharmaceuticals for positron emission tomography (PET), we have developed no-carrier-added m-(omega-[18F]fluoroalkyl)benzylguanidines. m-(omega-[18F]Fluoroalkyl)benzylguanidines were prepared in two steps starting from N,N'-bis(tert-butyloxycarbonyl)-N' '-(omega-methanesulfonyloxyalkyl)benzylguanidines in 20-30% radiochemical yields (decay corrected for 100 min) and with high radiochemical purity (>97%) and shown to be stable (>90%) in an in vitro metabolic stability assay. The binding of m-(3-[18F]fluoropropyl)benzylguanidine ((18F]3) to SK-N-SH human neuroblastoma cells was temperature dependent, and binding levels at 4 degrees C were reduced to half of that at 37 degrees C, which was similar to the reduction rate observed for [123I]MIBG. Tissue distribution studies in mice showed the highest uptake in the adrenals (%ID/g = 27.2 +/- 5.0%) with relatively high uptake in the myocardium (%ID/g = 9.3 +/- 0.5%). The results suggest that this radiotracer holds promise as a useful adrenomedullary radiopharmaceutical for PET imaging.

摘要

为了研究用于正电子发射断层扫描（PET）的肾上腺髓质放射性药物，我们制备了无载体添加的间位（ω-[¹⁸F]氟烷基）苄基胍。间位（ω-[¹⁸F]氟烷基）苄基胍由N,N'-双（叔丁氧羰基）-N''-（ω-甲磺酰氧基烷基）苄基胍分两步制备，放射化学产率为20%-30%（经100分钟衰变校正），放射化学纯度高（>97%），并且在体外代谢稳定性试验中显示稳定（>90%）。间位（3-[¹⁸F]氟丙基）苄基胍（[¹⁸F]3）与SK-N-SH人神经母细胞瘤细胞的结合具有温度依赖性，4℃时的结合水平降至37℃时的一半，这与[¹²³I]MIBG观察到的降低率相似。小鼠组织分布研究表明，肾上腺摄取最高（%ID/g = 27.2 ± 5.0%），心肌摄取相对较高（%ID/g = 9.3 ± 0.5%）。结果表明，这种放射性示踪剂有望成为一种用于PET成像的有用的肾上腺髓质放射性药物。