Department of Nuclear Medicine and PET, Prince of Wales Hospital, Sydney, Australia.
The Centenary Institute, University of Sydney, Sydney, Australia.
Eur J Nucl Med Mol Imaging. 2022 Oct;49(12):4037-4047. doi: 10.1007/s00259-022-05880-z. Epub 2022 Jul 2.
This study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with Ga ([Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death.
Five participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200-211 MBq) of [Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining.
[Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E - 02 ± 4.61E - 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology.
[Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial.
ACTRN12621000641897 (28/5/2021, retrospectively registered).
本研究评估了细胞死亡指示剂 [Ga]Ga-CDI 的人体生物分布、辐射剂量学、安全性和肿瘤摄取情况，[Ga]Ga-CDI 是一种新型放射性药物，可用于成像多种形式的细胞死亡。
招募了 5 名至少有一个颅外实体恶性肿瘤部位 > 2cm 且在研究前 8 周内无活动性癌症治疗的参与者。给参与者施用 205±4.1MBq（范围，200-211MBq）的 [Ga]Ga-CDI 和 8 次连续 PET 扫描：第一次立即开始，最后一次 3 小时后开始。监测参与者的临床、实验室和心电图副作用以及不良事件。测量尿液和血液放射性。在肿瘤、血池和器官上绘制球形感兴趣区，以确定生物分布并计算剂量学。在一名参与者中，使用末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色分析肿瘤标本中的细胞死亡情况。
[Ga]Ga-CDI 安全且耐受良好，无副作用或不良事件。[Ga]Ga-CDI 通过肾脏排泄，在其他器官中显示出低水平的生理性摄取，并且具有出色的成像特性。平均有效剂量为 2.17E-02±4.61E-03mSv/MBq。它可以成像组成性肿瘤细胞死亡，并与组织学上的肿瘤细胞死亡相关。
[Ga]Ga-CDI 是一种新型的细胞死亡成像放射性药物，安全、辐射剂量学低、生物分布和成像特性优异。与以前研究的用于成像细胞死亡的放射性药物相比，它具有潜在的优势，并已进展到概念验证试验。
ACTRN12621000641897（2021 年 5 月 28 日，回顾性注册）。
