首个人体评估 [F]CETO：一种新型的肾上腺皮质肿瘤示踪剂。
First-in-human evaluation of [F]CETO: a novel tracer for adrenocortical tumours.
机构信息
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Institute of Metabolic Science & Department of Medicine, University of Cambridge, Cambridge, UK.
出版信息
Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):398-409. doi: 10.1007/s00259-022-05957-9. Epub 2022 Sep 8.
PURPOSE
[C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[F]fluoroethyletomidate positron emission computed tomography ([F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.
METHODS
Fifteen patients underwent [F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.
RESULTS
Uptake of [F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K. Both K and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K, SUV, and SUV were 25, 22, and 17%.
CONCLUSIONS
High adrenal uptake combined with a low unspecific liver uptake suggests that F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate K.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083.
目的
[C]美替拉酮正电子发射断层扫描（PET）目前用于肾上腺皮质癌的分期和原发性醛固酮增多症（PA）的侧化。由于碳-11 的半衰期短，[C]美替拉酮在肝脏中的非特异性摄取率高，因此需要改进肾上腺成像方法。在之前的临床前研究中，已证明对氯-2-[F]氟乙基美替拉酮是一种特异性肾上腺示踪剂。目的是首次评估氯-2-[F]氟乙基美替拉酮正电子发射计算机断层扫描（[F]CETO-PET/CT）在肾上腺肿瘤患者和健康志愿者中的应用。
方法
15 例患者接受了[F]CETO-PET/CT 检查。招募了 5 名健康志愿者进行测试-重测分析，其中 3 名志愿者还接受了额外的[O]水 PET/CT 以测量肾上腺血流。进行了动脉采血和示踪剂代谢产物分析。评估了[F]CETO 的动力学，并通过与示踪剂动力学分析的结果测量值进行比较，验证了简化的定量方法。
结果
[F]CETO 在肝脏中的摄取量低，在肾上腺中的摄取量高。初始代谢迅速，随后达到平台期。健康肾上腺和除肾上腺皮质癌以外的所有肾上腺病变的[F]CETO 动力学最好用不可逆的单组织室模型来描述。标准化摄取值（SUV）与摄取率常数 K 密切相关。在健康对照组中，K 和 SUV 与肾上腺血流高度相关。K、SUV 和 SUV 的重复性系数分别为 25%、22%和 17%。
结论
高肾上腺摄取率与低非特异性肝脏摄取率相结合表明[F]CETO 是一种适合肾上腺成像的示踪剂。基于 1 小时后全身扫描的肾上腺 SUV 与净摄取率常数 K 密切相关。
试验注册
ClinicalTrials.gov，NCT05361083 于 2022 年 4 月 29 日进行了回顾性注册，网址为 https://clinicaltrials.gov/ct2/show/NCT05361083。
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