High-Contrast PET of Melanoma Using 18F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance
High-Contrast PET of Melanoma Using 18F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance
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DOI：
10.2967/jnumed.109.070060
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发表时间：
2010-03-01
影响因子：
9.3
通讯作者：
Hicks, Rodney J.
中科院分区：
文献类型：
--
作者：
Denoyer, Delphine;Greguric, Ivan;Hicks, Rodney J.
本研究的目的是评价新型探针F-18- 6氟- N-[2-（二乙基氨基）乙基]吡啶-3-甲酰胺（F-18-MEL 050）用于原发性和转移性黑色素瘤的成像。方法：在小鼠黑色素瘤模型中使用F-18-MEL 050进行PET。通过使用PET和高分辨率放射自显影术比较F-18-MEL 050在色素B16-F0同种异体移植肿瘤和人无色素A375异种移植物中的积累，研究了F-18-MEL 050的特异性。将F-18-MEL 050 PET结果与F-18-FDG PET（黑色素瘤分子成像的当前标准）进行比较。为了测试F-18-MEL 050评估黑色素瘤的转移性扩散的能力，通过PET/CT对肺转移的鼠模型进行成像，并且结果与肺中肿瘤负荷的物理评估相关。结果如下：在色素B16-F0移植物中，F-18-MEL 050 PET在1 h时产生的肿瘤与背景比约为20：1，在2 h和3 h时大于50：1。在B16-F0黑色素瘤同种异体移植物模型中，F-18-MEL 050的肿瘤与背景比率比F-18-FDG高9倍以上（50.9 +/- 6.9 vs. 5.8 +/- 0.5）。在无色素性黑素瘤异种移植物中未观察到摄取。在示踪剂注射后2小时，在PET上，在B16-BL 6荷瘤小鼠的肺中的转移性病灶中，F-18-MEL 050的强烈摄取是明显的，在PET/CT上的F-18-MEL 050积累与在尸检中确定的肿瘤负荷之间具有高度一致性。结论：F-18-MEL 050具有快速的肿瘤摄取和高保留，对黑色素具有特异性，这表明在疑似转移性黑色素瘤的无创临床评估中具有巨大潜力。
The aim of this study was to evaluate the novel probe F-18-6fluoro- N-[2-(diethylamino) ethyl] pyridine-3-carboxamide (F-18-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using F-18-MEL050 was performed in murine models of melanoma. The specificity of F-18-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. F-18-MEL050 PET results were compared with F-18-FDG PET, the current standard in melanoma molecular imaging. To test the ability of F-18-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. Results: In pigmented B16-F0 grafts, F-18-MEL050 PET yielded a tumor-to-background ratio of approximately 20: 1 at 1 h and greater than 50: 1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for F-18-MEL050 than for F-18-FDG (50.9 +/- 6.9 vs. 5.8 +/- 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of F-18-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor-bearing mice on PET at 2 h after tracer injection, with high concordance between F-18-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: F-18-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.