A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death,European Journal of Nuclear Medicine and Molecular Imaging

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A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2022-07-02 , DOI: 10.1007/s00259-022-05880-z
Ivan Ho Shon _{1,

2,

3} , Thomas Hennessy ₁ , Jennifer Guille ₁ , Michael P Gotsbacher ₄ , Angelina J Lay ₂ , Bruce McBride ₁ , Rachel Codd ₄ , Philip J Hogg ₂

Affiliation

Purpose

This study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with ⁶⁸Ga ([⁶⁸Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death.

Methods

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 [⁶⁸Ga]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.

Results

[⁶⁸Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [⁶⁸Ga]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.

Conclusion

[⁶⁸Ga]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.

Trial registration

ACTRN12621000641897 (28/5/2021, retrospectively registered)

中文翻译：

[68Ga]Ga-CDI 的首次人体研究：一种用于肿瘤细胞死亡成像的正电子发射放射性药物

目的

^{本研究评估了用68} Ga ([ ⁶⁸ Ga]Ga-CDI)标记的细胞死亡指示剂的人体生物分布、辐射剂量测定、安全性和肿瘤摄取，这是一种可以对多种形式的细胞死亡进行成像的新型放射性药物。

方法

招募了五名至少有一处颅外实体恶性肿瘤 > 2 cm 且在研究前 8 周内未接受积极癌症治疗的参与者。参与者接受了 205 ± 4.1 MBq（范围，200–211 MBq）的 [ ⁶⁸ Ga]Ga-CDI 和 8 次连续 PET 扫描：第一次立即开始，最后 3 小时后开始。监测参与者的临床、实验室和心电图副作用和不良事件。测量了尿液和血液的放射性。在肿瘤、血池和器官上绘制感兴趣的球形体积以确定生物分布并计算剂量测定。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) 染色分析肿瘤标本的细胞死亡情况。

结果

[ ⁶⁸ Ga]Ga-CDI 安全且耐受性良好，没有副作用或不良事件。[ ⁶⁸ Ga]Ga-CDI 经肾脏排泄，在其他器官中表现出低水平的生理吸收，并具有出色的成像特性。平均有效剂量为 2.17E − 02 ± 4.61E − 03 mSv/MBq。它对组成性肿瘤细胞死亡进行成像，并在组织学上与肿瘤细胞死亡相关联。