Purpose:

As stereotactic radiosurgery (SRS) and immunotherapy are increasingly used to treat brain metastases, incidence of radiation necrosis (RN) is consequently rising. Differentiating tumor regrowth (TR) from RN is vital in management but difficult to assess using MRI. We hypothesized that tumor methionine levels would be elevated given increased metabolism and high amino acid uptake, whereas RN would increase inflammation marked by upregulated translocator protein (PBR-TSPO), which can be quantified with specific PET tracers.

Procedures:

We performed a feasibility study to prospectively evaluate [¹¹C]methionine and [¹¹C]PBR28 using PET in 5 patients with 7 previously SRS-treated brain metastases demonstrating regrowth to differentiate TR from RN.

Results:

Sequential imaging with dual tracers was well-tolerated. [¹¹C]methionine was accurate for detecting pathologically confirmed TR in 7/7 lesions, whereas [¹¹C]PBR28 was only accurate in 3/7 lesions. Tumor PBR-TSPO expression was elevated in both melanoma and lung cancer cells, contributing to lack of specificity of [¹¹C]PBR28-PET.

Conclusion:

Sequential use of PET tracers is safe and effective. [¹¹C]Methionine was a reliable TR marker, but [¹¹C]PBR28 was not a reliable marker of RN. Studies are needed to determine the causes of post-radiation inflammation and identify specific markers of RN to improve diagnostic imaging.

中文翻译：

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[11C] 蛋氨酸和 [11C]PBR28 作为 PET 成像示踪剂以区分转移性肿瘤复发或辐射坏死

目的：

随着立体定向放射外科 (SRS) 和免疫疗法越来越多地用于治疗脑转移，放射坏死 (RN) 的发生率因此上升。区分肿瘤再生长 (TR) 和 RN 在管理中至关重要，但难以使用 MRI 进行评估。我们假设肿瘤甲硫氨酸水平会因代谢增加和氨基酸摄取增加而升高，而 RN 会增加以上调易位蛋白 (PBR-TSPO) 为标志的炎症，这可以用特定的 PET 示踪剂进行量化。

程序：

我们进行了一项可行性研究，在 5 名先前接受过 SRS 治疗的脑转移患者中使用 PET前瞻性地评估 [ ¹¹ C] 蛋氨酸和 [ ¹¹ C] PBR28，这些患者显示出可以通过再生长来区分 TR 和 RN。

结果：

使用双示踪剂进行的连续成像具有良好的耐受性。[ ¹¹ C] 蛋氨酸可准确检测 7/7 病变中经病理证实的 TR，而 [ ¹¹ C] PBR28 仅在 3/7 病变中准确。黑色素瘤和肺癌细胞中的肿瘤 PBR-TSPO 表达均升高，导致 [ ¹¹ C] PBR28-PET缺乏特异性。

结论：

连续使用 PET 示踪剂是安全有效的。[ ¹¹ C]蛋氨酸是可靠的TR标记物，但[ ¹¹ C]PBR28不是RN的可靠标记物。需要进行研究以确定放射后炎症的原因并确定 RN 的特定标志物以改善诊断成像。