Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C351, 10 Center Drive, MSC 1003, Bethesda, MD, 20892-1003, USA.
EJNMMI Res. 2013 Jan 12;3(1):3. doi: 10.1186/2191-219X-3-3.
The characterization of fast-decaying radiotracers that are labeled with carbon-11 (t1/2 = 20.38 min), including critical measurement of specific radioactivity (activity per mole at a specific time) before release for use in positron-emission tomography (PET), has relied heavily on chromatographic plus radiometric measurements, each of which may be vulnerable to significant errors. Thus, we aimed to develop a mass-specific detection method using sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) for identifying 11C-labeled tracers and for verifying their specific radioactivities.
The LC-MS/MS was tuned and set up with methods to generate and measure the product ions specific for carbon-11 species and M + 1 carrier (predominantly the carbon-13 isotopologue) in four 11C-labeled tracers. These radiotracers were synthesized and then analyzed before extensive carbon-11 decay. The peak areas of carbon-11 species and M + 1 carrier from the LC-MS/MS measurement and the calculated abundances of carbon-12 carrier and M + 1 radioactive species gave the mole fraction of carbon-11 species in each sample. This value upon multiplication with the theoretical specific radioactivity of carbon-11 gave the specific radioactivity of the radiotracer.
LC-MS/MS of each 11C-labeled tracer generated the product ion peaks for carbon-11 species and M + 1 carrier at the expected LC retention time. The intensity of the radioactive peak diminished as time elapsed and was undetectable after six half-lives of carbon-11. Measurements of radiotracer-specific radioactivity determined solely by LC-MS/MS at timed intervals gave a half-life for carbon-11 (20.43 min) in excellent agreement with the value obtained radiometrically. Additionally, the LC-MS/MS measurement gave specific radioactivity values (83 to 505 GBq/μmol) in good agreement with those from conventional radiometric methods.
11C-Labeled tracers were characterized at a fundamental level involving isolation and mass detection of extremely low-abundance carbon-11 species along with the M + 1 carrier counterpart. This LC-MS/MS method for characterizing fast-decaying radiotracers is valuable in both the development and production of PET radiopharmaceuticals.
用碳-11（t1/2=20.38 分钟）标记的快速衰减放射性示踪剂的特性，包括在用于正电子发射断层扫描（PET）之前释放之前对其比放射性（特定时间的每摩尔活性）进行关键测量，主要依赖于色谱法和放射性测量，每种方法都可能容易出现重大误差。因此，我们旨在开发一种使用灵敏的液相色谱-质谱/质谱（LC-MS/MS）进行质量特异性检测的方法，用于识别 11C 标记的示踪剂并验证其比放射性。
LC-MS/MS 经过调整和设置，可生成和测量四个 11C 标记示踪剂中特定于碳-11 种的产物离子和 M+1 载体（主要是碳-13 同位素）。这些放射性示踪剂在广泛的碳-11 衰变之前进行了合成和分析。从 LC-MS/MS 测量得出的碳-11 种和 M+1 载体的峰面积以及计算得出的碳-12 载体和 M+1 放射性种的丰度给出了每个样品中碳-11 种的摩尔分数。该值乘以碳-11 的理论比放射性，得到放射性示踪剂的比放射性。
每个 11C 标记示踪剂的 LC-MS/MS 均在预期的 LC 保留时间处生成碳-11 种和 M+1 载体的产物离子峰。随着时间的流逝，放射性峰的强度减弱，在六个碳-11 的半衰期后无法检测到。仅通过 LC-MS/MS 在定时间隔测量放射性示踪剂的比放射性会给出碳-11 的半衰期（20.43 分钟），与放射性测量获得的值非常吻合。此外，LC-MS/MS 测量给出的比放射性值（83 至 505GBq/μmol）与传统放射性方法非常吻合。
对涉及极其低丰度碳-11 种与 M+1 载体的分离和质量检测的 11C 标记示踪剂进行了基础水平的表征。这种用于快速衰减放射性示踪剂特性的 LC-MS/MS 方法在 PET 放射性药物的开发和生产中都很有价值。
