123I-BZA2 as a Melanin-Targeted Radiotracer for the Identification of Melanoma Metastases: Results and Perspectives of a Multicenter Phase III Clinical Trial
123I-BZA2 as a Melanin-Targeted Radiotracer for the Identification of Melanoma Metastases: Results and Perspectives of a Multicenter Phase III Clinical Trial
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DOI：
10.2967/jnumed.113.123554
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发表时间：
2014-01-01
影响因子：
9.3
通讯作者：
D'Incan, Michel
中科院分区：
文献类型：
--
作者：
Cachin, Florent;Miot-Noirault, Elisabeth;D'Incan, Michel
我们团队开发了一种新的放射性药物--123I-N-(2二乙氨基乙基)-2-碘苯甲酰胺(123I-BZA2)，它是一种能够与黑色素瘤细胞中的黑色素结合的苯甲酰胺衍生物。在一项前瞻性和多中心的III期临床研究中，比较了18F-FDGPET/CT和123I-BZA2核素显像在黑色素瘤分期中的价值。方法：有皮肤或眼部黑色素瘤病史的患者来自8家医院。18F-FDG显像按标准的正电子发射计算机断层扫描方法进行。在注射2MBq/kg剂量的123I-BZA2后4h，采集全身、静态平面和SPECT/CT(如果有)图像。计算并比较18F-FDG和123I-BZA2诊断黑色素瘤转移的敏感性和特异性。在临床随访6个月后或根据病变活检(如果有)，确定真阳性和真阴性病变状态。活检组织的黑色素含量用标准的Fontana-Masson银法进行评估，并与123IBZA2摄取相关。根据统计分析，夹杂物的数量估计为186。结果：从2008年到2010年，共有87名患者入选。其中45例(52%)有转移。总共分析了338个影像异常；86个病变被认为是转移的，25个病变活检中有20个发现了黑色素瘤转移。在以患者为基础的分析中，18F-FDG诊断黑色素瘤转移的敏感性高于123I-BZA2，分别为87%和39%(P，0.05)。18F-FDG和123I-BZA2的特异性差异无统计学意义，分别为78%和94%。在基于病变的分析中，18F-FDG的敏感性显著高于123I-BZA2(80%对23%，P<0.05)。18F-FDG的特异性低于123I-BZA2(54%比86%，P<0.05)。根据活检分析，20个转移灶中只有9个(45%)黑色素含量较高。~(123)I-BZA2显像在8个黑色素阳性病灶中有6个阳性，在10个黑色素阴性病灶中有3个相当阳性，在10个黑色素阴性病灶中有7个是阴性。123I-BZA2诊断黑色素阳性病变的敏感性和特异性分别为75%和70%。由于123I-BZA2敏感性较低，这项临床试验在纳入87名患者后提前结束。结论：本研究证实了18F-FDGPET/CT对黑色素瘤分期的价值，并增强了123I-BZA2对黑色素阳性转移性黑色素瘤诊断的高准确性。此外，标记有治疗性放射性核素的苯甲酰胺衍生物可能为治疗黑色素阳性转移的转移性黑色素瘤患者提供一种新的策略。
Our group has developed a new radiopharmaceutical, 123I-N-(2diethylaminoethyl)- 2-iodobenzamide (123I-BZA2), a benzamide derivative able to bind to melanin pigment in melanoma cells. In a prospective and multicentric phase III clinical study, the value of 18F-FDG PET/CT and 123I-BZA2 scintigraphy was compared for melanoma staging. Methods: Patients with a past history of cutaneous or ocular melanoma were included from 8 hospitals. 18F-FDG imaging was performed according to a standard PET protocol. Whole-body, static planar, and SPECT/CT (if available) images were acquired 4 h after injection of a 2 MBq/kg dose of 123I-BZA2. 18F-FDG and 123I-BZA2 sensitivity and specificity for the diagnosis of melanoma metastasis were calculated and compared on both a lesion basis and a patient basis. True-positive and true-negative lesion status was determined after 6 mo of clinical follow-up or according to lesion biopsies (if available). Melanin content in biopsies was evaluated with the standard Fontana-Masson silver method and was correlated with 123IBZA2 uptake. Based on statistical analysis, the number of inclusions was estimated at 186. Results: In all, 87 patients were enrolled from 2008 to 2010. Of these, 45 (52%) had metastases. A total of 338 imaging abnormalities were analyzed; 86 lesions were considered metastases, and 20 of 25 lesion biopsies found melanoma metastases. In a patient-based analysis, the sensitivity of 18F-FDG for diagnosis of melanoma metastases was higher than that of 123I-BZA2, at 87% and 39%, respectively (P, 0.05). For specificity, 18F-FDG and 123I-BZA2 were not statistically different, at 78% and 94%, respectively. In a lesion-based analysis, the sensitivity of 18F-FDG was statistically higher than that of 123I-BZA2 (80% vs. 23%, P, 0.05). The specificity of 18F-FDG was lower than that of 123I-BZA2 (54% vs. 86%, P, 0.05). According to biopsy analysis, only 9 of 20 metastatic lesions (45%) were pigmented with high melanin content. 123I-BZA2 imaging was positive for 6 of 8 melanin-positive lesions, fairly positive for 3 of 10 melanin-negative lesions, and negative for 7 of 10 melaninnegative lesions. The sensitivity and specificity of 123I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively. Because of a low 123I-BZA2 sensitivity, this clinical trial was prematurely closed after 87 patients had been included. Conclusion: This study confirms the value of 18F-FDG PET/CT for melanoma staging and strengthens the high accuracy of 123I-BZA2 for diagnosis of melanin-positive metastatic melanoma. Moreover, benzamide derivatives radiolabeled with therapeutic radionuclide may offer a new strategy for the treatment of metastatic melanoma patients harboring melanin-positive metastases.