Nardelli Anna, Castaldi Elena, Ortosecco Giovanni, Speranza Antonio, Storto Giovanni, Pace Leonardo, Salvatore Marco
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
Appl Radiat Isot. 2011 Jan;69(1):52-5. doi: 10.1016/j.apradiso.2010.09.001. Epub 2010 Sep 8.
Peptide receptor radionuclide therapy (PRRT) has recently expanded due to radiolabelling of DOTA-peptides, such as the somatostatin analogues [DOTA(0), Tyr(3)]octreotate (DOTATATE). The achievement of high specific activities during procedures has been indicated as the critical factor to consent effective therapy. Several radiochemical factors may negatively impact reaction procedures such as pH, temperature and time of reaction. Our study was undertaken to explore the influence of radiochemical parameters, such as time of incubation, on reaction kinetics during the radiolabelling of DOTATATE with (90)Y.
Forty-five radiolabelling procedures were carried out using small volumes of yttrium-90, typically 60-78 μL. At nearly constant pH and temperature two different settings of radiolabelling procedures were implemented, removing the products from the heating water bath approximately after 30 min (group E, early; n=20) and after 39 min (group L, later; n=25). Quality controls were performed by means of both high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC).
Reaction kinetics for (90)Y were found to a provide suitable percentage of incorporation at pH 4.5 for both groups. Reaction temperature was not different between groups E and L. A significant difference was found between the two groups in radiochemical yield, which was 95.6% ± 0.8 for group E and 98.2% ± 1.1 for group L (p<0.0001). The specific activity of the final product was 46.9 MBq/nmol.
In order to achieve optimal specific activities, pH, temperature and time of reaction necessitate careful evaluation and setting. A statistically significant difference in labelling yield was found between a set of procedures completed at 39 min as compared to that executed at 30 min, keep the reaction pH and temperature constant.
由于DOTA肽（如生长抑素类似物[DOTA(0),Tyr(3)]奥曲肽（DOTATATE））的放射性标记，肽受体放射性核素治疗（PRRT）最近得到了扩展。在操作过程中实现高比活度被认为是实现有效治疗的关键因素。几个放射化学因素可能会对反应过程产生负面影响，如pH值、温度和反应时间。我们的研究旨在探讨放射化学参数（如孵育时间）对用（90）Y标记DOTATATE过程中反应动力学的影响。
使用小体积的钇-90（通常为60-78μL）进行了45次放射性标记操作。在几乎恒定的pH值和温度下，实施了两种不同的放射性标记操作设置，分别在约30分钟后（E组，早期；n=20）和39分钟后（L组，晚期；n=25）从加热水浴中取出产物。通过高效液相色谱（HPLC）和薄层色谱（TLC）进行质量控制。
发现（90）Y的反应动力学在pH 4.5时为两组提供了合适的掺入百分比。E组和L组之间的反应温度没有差异。两组之间在放射化学产率上存在显著差异，E组为95.6%±0.8，L组为98.2%±1.1（p<0.0001）。最终产物的比活度为46.9 MBq/nmol。
为了实现最佳比活度，需要仔细评估和设置反应的pH值、温度和时间。在保持反应pH值和温度恒定的情况下，发现一组在39分钟完成的操作与在30分钟完成的操作相比，标记产率存在统计学上的显著差异。
