Vaalburg W, Coenen H H, Crouzel C, Elsinga P H, Långström B, Lemaire C, Meyer G J
Department of Nuclear Medicine, University Hospital, Groningen, The Netherlands.
Int J Rad Appl Instrum B. 1992 Feb;19(2):227-37. doi: 10.1016/0883-2897(92)90011-m.
In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1-11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2-18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose.
原则上，正电子发射断层扫描（PET）结合用正电子发射放射性核素标记的氨基酸和动力学代谢模型，可在体内定量组织中的局部蛋白质合成速率。这些PET测量在例如肿瘤学、神经病学和精神病学等领域具有临床应用潜力。用于测量蛋白质合成速率（PSR）的最佳正电子发射氨基酸应具有高蛋白质掺入率，能通过自动化设备轻松制备，且非蛋白质放射性代谢物最少。目前，L-[甲基-¹¹C]蛋氨酸、L-[¹-¹¹C]亮氨酸、L-[¹-¹¹C]酪氨酸、L-[¹-¹¹C]苯丙氨酸、L-[¹-¹¹C]蛋氨酸和L-[²-¹⁸F]氟酪氨酸正在正常志愿者和/或患者中进行评估。还提出了其他几种氨基酸。目前尚无关于不同氨基酸在人体临床实用性的比较。由于¹⁸F的半衰期比¹¹C长，[¹⁸F]氟氨基酸在研究蛋白质合成相对缓慢的组织（如脑）以及在配备场外但附近有回旋加速器的机构中应用时，可能比[¹¹C]氨基酸具有优势。[¹³N]氨基酸的半衰期被认为太短，不适合灵活的临床应用。目前尚未对[¹³N]氨基酸的代谢区室模型进行研究。对于常规应用，可靠地制备放射性药物至关重要。在所有正在评估的氨基酸中，只有L-[甲基-¹¹C]蛋氨酸有可靠、高产率、易于自动化的生产程序。然而，由于其非蛋白质代谢，这种示踪剂不太可能准确测量PSR。对于其他氨基酸，生产中的主要问题与复杂的多步合成和/或低放射化学产率、复杂的纯化方法以及分离L-对映体的需求有关。正在研究的动力学代谢模型根据补偿标记代谢物的必要性由4或5个区室组成。氨基酸的代谢概况主要从动物实验中提取。由于血浆中标记代谢物的数量和量，[¹¹C]羧基标记的氨基酸比在其他位置含有碳-¹¹的氨基酸更受青睐。目前，对于体内测量PSR的最佳标记氨基酸以及为此目的报道的氨基酸制备方法，尚无推荐意见。
