Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for Imaging xC Transporter Using Positron Emission Tomography in Patients with Non-Small Cell Lung or Breast Cancer
Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for Imaging xC Transporter Using Positron Emission Tomography in Patients with Non-Small Cell Lung or Breast Cancer
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DOI：
10.1158/1078-0432.ccr-12-0214
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发表时间：
2012-10-01
影响因子：
11.5
通讯作者：
Moon, Dae Hyuk
中科院分区：
文献类型：
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作者：
Baek, Sora;Choi, Chang-Min;Moon, Dae Hyuk
目的：（4S）-4-（3-[F-18]fluoropropyl）-L-谷氨酸（BAY 94-9392，alias [F-18]FSPG）是一种新的用正电子发射断层扫描（PET）成像x（C）（-）转运蛋白活性的示踪剂。我们的目的是探索[F-18]FSPG相对于2-[F-18]氟-2-脱氧葡萄糖（[F-18]FDG）在患者中的肿瘤检出率。[F-18]FSPG摄取与x（C）（-）转运蛋白和CD 44免疫组化表达的相关性也进行了分析，CD 44稳定了系统x（C）（-）的xCT亚基。注射约300 MBq[F-18]FSPG后采集PET图像。结果：[F-18] FSPG PET显示肾脏和胰腺的高摄取，血液清除迅速。[F-18]FSPG确定了所有10个NSCLC和5个经病理学证实的乳腺癌病变中的3个。[F-18] FSPG检测到NSCLC中67个[F-18]FDG病灶中的59个（88%），乳腺癌中73个病灶中的30个（41%）。在NSCLC中仅在[F-18] FSPG上额外检测到7个病变。非小细胞肺癌与[F-18]FDG的肿瘤/血池标准化摄取值（SUV）比值无显著性差异，而乳腺癌的SUV比值显著低于[F-18]FDG（P < 0.05）。[F-18] FSPG的最大SUV与x（C）（-）转运体和CD 44的免疫组化染色强度显著相关（P < 0.01）。结论：[F-18]FSPG在NSCLC中有较高的肿瘤检出率，是一种有前途的示踪剂。[F-18]FSPG PET可评估癌症患者的x（C）（-）转运蛋白活性。临床癌症研究; 18（19）; 5427-37。（C）2012年AACR。
Purpose: (4S)-4-(3-[F-18]fluoropropyl)-L-glutamate (BAY 94-9392, alias [F-18]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [F-18]FSPG in patients relative to 2-[F-18]fluoro-2-deoxyglucose ([F-18]FDG). The correlation of [F-18]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed.Experimental Design: Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [F-18]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq[F-18]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody.Results: [F-18] FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [F-18]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [F-18] FSPG detected 59 of 67 (88%) [F-18]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [F-18] FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [F-18]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [F-18] FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01).Conclusions: [F-18]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [F-18]FSPG PET may assess x(C)(-) transporter activity in patients with cancer. Clin Cancer Res; 18(19); 5427-37. (C)2012 AACR.