Purpose

Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [¹⁸F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy.

Methods

[¹⁸F]d₄-FET was synthesised by two automated radiochemistry modules. Biodistribution studies and imaging efficacy were evaluated in vivo and ex vivo in rodent models, while metabolic stability and radiation dosimetry were assessed in non-human primates. Additionally, preliminary imaging evaluations were carried out in five brain tumor patients: three glioma patients underwent imaging with both [¹⁸F]d₄-FET and [¹⁸F]FET, and two patients with brain metastases were imaged using [¹⁸F]d₄-FET and [¹⁸F]FDG.

Results

[¹⁸F]d₄-FET demonstrated high radiochemical purity and yield. PET/MRI in rodent models demonstrated superior TBR for [¹⁸F]d₄-FET compared to [¹⁸F]FET, and autoradiography showed tumor margins that correlated well with pathological extents. Studies in cynomolgus monkeys indicated comparable in vivo stability and effective dose with [¹⁸F]FET. In glioma patients, [¹⁸F]d₄-FET showed enhanced TBR, while in patients with brain metastases, [¹⁸F]d₄-FET displayed superior lesion delineation compared to [¹⁸F]FDG, especially in smaller metastatic sites.

Conclusion

We successfully synthesized the novel PET radiotracer [¹⁸F]d₄-FET, which retains the advantageous properties of [¹⁸F]FET while potentially enhancing TBR for glioma imaging. Preliminary studies indicate excellent stability, efficacy, and sensitivity of [¹⁸F]d₄-FET, suggesting its potential in clinical evaluations of brain tumors.

Trial registration

ChiCTR2400081576, registration date: 2024–03-05, https://www.chictr.org.cn/bin/project/edit?pid=206162

中文翻译：

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用于脑肿瘤成像的 [18F]d4-FET 的合成、临床前评估和首次人体研究

 目的

肿瘤背景比 （TBR） 是肿瘤 PET 成像中的一个关键指标。本研究旨在通过用氘 （“D”） 代替氢 （“H”） 来提高 [¹⁸F]FET 在脑肿瘤成像中的 TBR，从而提高诊断的灵敏度和准确性。

 方法

[¹⁸个地址]d_4-FET 由两个自动放射化学模块合成。在啮齿动物模型中评估了体内和离体的生物分布研究和成像效果，同时在非人灵长类动物中评估了代谢稳定性和辐射剂量测定。此外，对 5 名脑肿瘤患者进行了初步影像学评估： 3 名胶质瘤患者接受了 [¹⁸F]d_4-FET 和 [¹⁸F]FET 的影像学检查，2 名脑转移患者使用 [¹⁸F]d_4-FET 和 [¹⁸F]FDG 进行成像。

 结果

[¹⁸个地址]d_4-FET 表现出高放射化学纯度和产率。啮齿动物模型中的 PET/MRI 显示 [¹⁸F]d_4-FET 的 TBR 优于 [¹⁸F]FET，放射自显影显示肿瘤边缘与病理范围密切相关。对食蟹猴的研究表明，与 [¹⁸F]FET 的体内稳定性和有效剂量相当。在神经胶质瘤患者中，[¹⁸F]d_4-FET 显示增强的 TBR，而在脑转移患者中，[¹⁸F]d_4-FET 与 [¹⁸F]FDG 相比表现出更好的病变描绘，尤其是在较小的转移部位。

 结论

我们成功合成了新型 PET 放射性示踪剂 [¹⁸F]d_4-FET，它保留了 [¹⁸F]FET 的有利特性，同时可能增强神经胶质瘤成像的 TBR。初步研究表明 [¹⁸F]d_4-FET 具有出色的稳定性、有效性和敏感性，表明其在脑肿瘤临床评估中的潜力。

 试用注册

ChiCTR2400081576，注册日期：2024–03-05，https://www.chictr.org.cn/bin/project/edit?pid=206162