Wester H J, Willoch F, Tölle T R, Munz F, Herz M, Oye I, Schadrack J, Schwaiger M, Bartenstein P
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
J Nucl Med. 2000 Jul;41(7):1279-86.
6-O(2-[18F]fluoroethyl)-6- -desmethyldiprenorphine ([18F]DPN) was developed and biologically evaluated. Results of animal experiments, binding studies in vivo, and a human PET study are reported and compared with those of [11C]DPN.
[18F]DPN was obtained by 18F-fluoroethylation of 3-O-trityl-6-O-desmethyldiprenorphine and subsequent deprotection in good radiochemical yields (23% +/- 7%; 100 min; 37 TBq/mmol). Binding of [18F]DPN to mu, kappa, and delta opioid receptors was shown by autoradiography studies on rat brain slices. Quantification of cerebral opioid receptor binding in men was performed by spectral analysis of a dynamic PET scan (25 frames, 90 min) after intravenous application of 63 MBq [18F]DPN (36 GBq/micromol) and correction for metabolites.
[18F]DPN shows high affinity to opioid receptors. Parametric images (impulse response function at 60 min) of this human study showed a binding pattern of [18F]DPN equal to that of a control group (n = 9 healthy volunteers) after administration of [11C]DPN.
The advantage of the longer half-life of 18F will allow extended scanning periods, more flexible interventions (e.g., displacement studies), and DPN to be available to PET centers without an on-site cyclotron.
6 - O(2 - [¹⁸F]氟乙基)-6 - 去甲基二丙诺啡([¹⁸F]DPN)已被研发并进行生物学评估。报告了动物实验、体内结合研究以及一项人体PET研究的结果，并与[¹¹C]DPN的结果进行了比较。
[¹⁸F]DPN通过3 - O - 三苯甲基 - 6 - O - 去甲基二丙诺啡的¹⁸F - 氟乙基化及后续脱保护反应制得，放射化学产率良好(23%±7%；100分钟；37 TBq/mmol)。通过对大鼠脑切片的放射自显影研究显示了[¹⁸F]DPN与μ、κ和δ阿片受体的结合。在静脉注射63 MBq [¹⁸F]DPN(36 GBq/μmol)并对代谢物进行校正后，通过动态PET扫描(25帧，90分钟)的光谱分析对男性大脑阿片受体结合进行定量。
[¹⁸F]DPN对阿片受体显示出高亲和力。这项人体研究的参数图像(60分钟时的脉冲响应函数)显示，给予[¹¹C]DPN后，[¹⁸F]DPN的结合模式与对照组(n = 9名健康志愿者)相同。
¹⁸F较长半衰期的优势将允许延长扫描时间、进行更灵活的干预(如置换研究)，并且使PET中心无需现场回旋加速器就能获得DPN。
