Mena Esther, Owenius Rikard, Turkbey Baris, Sherry Richard, Bratslavsky Gennady, Macholl Sven, Miller Matthew P, Somer Ed J, Lindenberg Liza, Adler Stephen, Shih Joanna, Choyke Peter, Kurdziel Karen
Molecular Imaging Program, NCI, NIH, Bethesda, MD, USA.
Eur J Nucl Med Mol Imaging. 2014 Oct;41(10):1879-88. doi: 10.1007/s00259-014-2791-x. Epub 2014 Jun 28.
PURPOSE: [(18)F]Fluciclatide is an integrin-targeted PET radiopharmaceutical. αvβ3 and αvβ5 are upregulated in tumor angiogenesis as well as on some tumor cell surfaces. Our aim was to use [(18)F]fluciclatide (formerly known as [(18)F]AH111585) for PET imaging of angiogenesis in melanoma and renal tumors and compare with tumor integrin expression. METHODS: Eighteen evaluable patients with solid tumors ≥2.0 cm underwent [(18)F]fluciclatide PET/CT. All patients underwent surgery and tumor tissue samples were obtained. Immunohistochemical (IHC) staining with mouse monoclonal antibodies and diaminobenzidine (DAB) was applied to snap-frozen tumor specimens, and additional IHC was done on formalin-fixed paraffin-embedded samples. DAB optical density (OD) data from digitized whole-tissue sections were compared with PET SUV80% max, and Patlak influx rate constant (K i) data, tumor by tumor. RESULTS: Tumors from all 18 patients demonstrated measurable [(18)F]fluciclatide uptake. At the final dynamic time-point (55 min after injection), renal malignancies (in 11 patients) demonstrated an average SUV80% max of 6.4 ± 2.0 (range 3.8 - 10.0), while the average SUV80% max for metastatic melanoma lesions (in 6 patients) was 3.0 ± 2.0 (range 0.7 - 6.5). There was a statistically significant difference in [(18)F]fluciclatide uptake between chromophobe and nonchromophobe renal cell carcinoma (RCCs, with SUV80% max of 8.2 ± 1.8 and 5.4 ± 1.4 (P = 0.020) and tumor-to-normal kidney (T/N) ratios of 1.5 ± 0.4 and 0.9 ± 0.2, respectively (P = 0.029). The highest Pearson's correlation coefficients were obtained when comparing Patlak K i and αvβ5 OD when segregating the patient population between melanoma and RCC (r = 0.83 for K i vs. melanoma and r = 0.91 for K i vs. RCC). SUV80% max showed a moderate correlation with αvβ5 and αvβ3 OD. CONCLUSION: [(18)F]Fluciclatide PET imaging was well tolerated and demonstrated favorable characteristics for imaging αvβ3 and αvβ5 expression in melanoma and RCC. Higher uptake was observed in chromophobe than in nonchromophobe RCC. [(18)F]Fluciclatide may be a useful radiotracer to improve knowledge of integrin expression.
目的：[（18）F]氟西拉肽是一种靶向整合素的PET放射性药物。αvβ3和αvβ5在肿瘤血管生成以及某些肿瘤细胞表面上调。我们的目的是使用[（18）F]氟西拉肽（以前称为[（18）F]AH111585）对黑色素瘤和肾肿瘤中的血管生成进行PET成像，并与肿瘤整合素表达进行比较。 方法：18例可评估的实体瘤≥2.0 cm的患者接受了[（18）F]氟西拉肽PET/CT检查。所有患者均接受手术并获取肿瘤组织样本。对速冻肿瘤标本应用小鼠单克隆抗体和二氨基联苯胺（DAB）进行免疫组织化学（IHC）染色，并在福尔马林固定石蜡包埋样本上进行额外的IHC。将数字化全组织切片的DAB光密度（OD）数据与PET SUV80%最大值以及Patlak流入速率常数（K i）数据逐肿瘤进行比较。 结果：所有18例患者的肿瘤均显示出可测量的[（18）F]氟西拉肽摄取。在最终动态时间点（注射后55分钟），肾恶性肿瘤（11例患者）的平均SUV80%最大值为6.4±2.0（范围3.8 - 10.0），而转移性黑色素瘤病变（6例患者）的平均SUV80%最大值为3.0±2.0（范围0.7 - 6.5）。嫌色性和非嫌色性肾细胞癌（RCC）之间的[（18）F]氟西拉肽摄取存在统计学显著差异（SUV80%最大值分别为8.2±1.8和5.4±1.4（P = 0.020），肿瘤与正常肾脏（T/N）比值分别为1.5±0.4和0.9±0.2（P = 0.029）。当将患者群体分为黑色素瘤和RCC时，比较Patlak K i和αvβ5 OD时获得最高的Pearson相关系数（黑色素瘤的K i与αvβ5的r = 0.83，RCC的K i与αvβ5的r = 0.91）。SUV80%最大值与αvβ5和αvβ3 OD呈中度相关。 结论：[（18）F]氟西拉肽PET成像耐受性良好，并显示出在黑色素瘤和RCC中对αvβ3和αvβ5表达成像的良好特性。嫌色性RCC中的摄取高于非嫌色性RCC。[（18）F]氟西拉肽可能是一种有用的放射性示踪剂，可提高对整合素表达的认识。
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