Leece Alicia K, Heidari Pedram, Yokell Daniel L, Mahmood Umar
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Appl Radiat Isot. 2013 Oct;80:99-102. doi: 10.1016/j.apradiso.2013.06.019. Epub 2013 Jun 24.
Often peptides used in synthesis of radiopharmaceutical PET tracers are lipophilic and adhere to the walls of container closure systems (CCS) such that costly peptide and product are not fully recoverable after synthesis occurs. This investigation compares a standard United States Pharmacopeia (USP) Type I borosilicate glass CCS to a cyclic polyolefin copolymer Crystal Zenith(®) (CZ) CCS, for (68)Ga-chloride and (68)Ga-DOTATOC ([(68)Ga] Ga-DOTA-D-Phe1-Tyr3-octreotide) retention in the reaction vial after labeling.
(68)Gallium labeling of DOTATOC was conducted by adding (68)Ga-chloride, 2M HEPES (4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid) or 0.75 M sodium acetate, and 1-30 µg of DOTATOC into the CZ or glass CCS. The reaction mixture was heated for 15 min and cooled to room temperature. The crude reaction mixture was then withdrawn via syringe, for final processing. The CCS was then assayed using a dose calibrator to determine the amount of retained (68)Ga-DOTATOC. Statistical significance was assessed using an unpaired Student's t-test.
In all experiments (n=72) with various amounts of peptide and different buffering systems, the CZ CCS retained less activity than the glass CCS. Using 2 M HEPES and 15 µg or 30 µg of DOTATOC, the CZ CCS retained approximately 10% less of the labeled DOTATOC compared to the glass CCS (p<0.05). Utilizing either a sodium acetate or a HEPES buffering system with 15 µg or 30 µg of DOTATOC, the CZ CCS retained approximately 2.5% less of the total reaction activity compared to the glass CCS (p<0.05). Product yield was equivalent in glass and CZ CCS under the same reaction conditions. Both the CZ and glass vials showed no retention of (68)Ga-chloride.
For applications involving the labeling of peptides such as (68)Ga-DOTATOC, the CZ CCS compared to the glass CCS, results in an improved recovery of product.
用于合成放射性药物正电子发射断层显像（PET）示踪剂的肽类通常具有亲脂性，会附着在容器密封系统（CCS）的壁上，以至于合成后昂贵的肽和产品无法完全回收。本研究比较了美国药典（USP）标准I型硼硅酸盐玻璃CCS与环状聚烯烃共聚物Crystal Zenith（®）（CZ）CCS对氯化（68）镓和（68）镓- DOTATOC（[(68)Ga] Ga-DOTA-D-Phe1-Tyr3-奥曲肽）在标记后反应瓶中的保留情况。
通过将氯化（68）镓、2M 4-（2-羟乙基）哌嗪-1-乙磺酸（HEPES）或0.75M醋酸钠以及1 - 30μg的DOTATOC加入到CZ或玻璃CCS中进行DOTATOC的（68）镓标记。将反应混合物加热15分钟，然后冷却至室温。然后通过注射器抽取粗反应混合物进行最终处理。然后使用剂量校准器对CCS进行分析，以确定保留的（68）镓- DOTATOC的量。使用非配对学生t检验评估统计学显著性。
在所有涉及不同肽量和不同缓冲系统的实验（n = 72）中，CZ CCS保留的活性低于玻璃CCS。使用2M HEPES和15μg或30μg的DOTATOC时，与玻璃CCS相比，CZ CCS保留的标记DOTATOC减少了约10%（p < 0.05）。使用醋酸钠或HEPES缓冲系统以及15μg或30μg的DOTATOC时，与玻璃CCS相比，CZ CCS保留的总反应活性减少了约2.5%（p < 0.05）。在相同反应条件下，玻璃和CZ CCS的产品产率相当。CZ和玻璃小瓶均未显示出对氯化（68）镓有保留。
对于涉及如（68）镓- DOTATOC等肽类标记的应用，与玻璃CCS相比，CZ CCS可提高产品回收率。
