123I-BZA2 as a melanin-targeted radiotracer for the identification of melanoma metastases: Results and perspectives of a multicenter phase III clinical trial

Abstract

Our group has developed a new radiopharmaceutical, 123I-N-(2- diethylaminoethyl)-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 - 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 ± 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 ± 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. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.