Current analytical methods for characterizing pharmacokinetic and metabolic properties of positron emission tomography (PET) and single photon emission computed tomography (SPECT) probes are limited. Alternative methods to study tracer metabolism are needed. The study objective was to assess the potential of high performance liquid chromatography - inductively coupled plasma - mass spectrometry (HPLC-ICP-MS) for quantification of molecular probe metabolism and pharmacokinetics using stable isotopes. Two known peptide-DOTA conjugates were chelated with natGa and natIn. Limit of detection of HPLC-ICP-MS for 69Ga and 115In was determined. Rats were administered 50–150 nmol of Ga- and/or In-labeled probes, blood was serially sampled, and plasma analyzed by HPLC-ICP-MS using both reverse phase and size exclusion chromatography. The limits of detection were 0.16 pmol for 115In and 0.53 pmol for 69Ga. Metabolites as low as 0.001 %ID/g could be detected and transchelation products identified. Simultaneous administration of Ga- and In-labeled probes allowed the determination of pharmacokinetics and metabolism of both probes in a single animal. HPLC-ICP-MS is a robust, sensitive and radiation-free technique to characterize the pharmacokinetics and metabolism of imaging probes.

中文翻译：

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使用 HPLC-ICP-MS 进行代谢物分析，作为成像探针体内表征的工具。

目前用于表征正电子发射断层扫描 (PET) 和单光子发射计算机断层扫描 (SPECT) 探针的药代动力学和代谢特性的分析方法是有限的。需要研究示踪剂代谢的替代方法。研究目的是评估高效液相色谱 - 电感耦合等离子体 - 质谱 (HPLC-ICP-MS) 在使用稳定同位素定量分子探针代谢和药代动力学方面的潜力。两种已知的肽-DOTA 缀合物与 natGa 和 natIn 螯合。确定了 HPLC-ICP-MS 对 69Ga 和 115In 的检测限。给大鼠施用 50–150 nmol Ga 和/或 In 标记的探针，对血液进行连续取样，并使用反相和尺寸排阻色谱通过 HPLC-ICP-MS 分析血浆。115In 的检测限为 0.16 pmol，69Ga 的检测限为 0.53 pmol。可以检测到低至 0.001 %ID/g 的代谢物并鉴定转螯合产物。同时施用 Ga 和 In 标记的探针可以在单个动物中测定两种探针的药代动力学和代谢。HPLC-ICP-MS 是一种可靠、灵敏且无辐射的技术，用于表征成像探针的药代动力学和代谢。