title: (123)I-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, (123)I - N-(2-diethylaminoethyl)-2-iodobenzamide ((123)I-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 (18)F-FDG PET/CT and (123)I-BZA2 scintigraphy was compared for melanoma staging.
  
  
  METHODS
  Patients with a past history of cutaneous or ocular melanoma were included from 8 hospitals. (18)F-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 (123)I-BZA2. (18)F-FDG and (123)I-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 (123)I-BZA2 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 (18)F-FDG for diagnosis of melanoma metastases was higher than that of (123)I-BZA2, at 87% and 39%, respectively (P < 0.05). For specificity, (18)F-FDG and (123)I-BZA2 were not statistically different, at 78% and 94%, respectively. In a lesion-based analysis, the sensitivity of (18)F-FDG was statistically higher than that of (123)I-BZA2 (80% vs. 23%, P < 0.05). The specificity of (18)F-FDG was lower than that of (123)I-BZA2 (54% vs. 86%, P < 0.05). According to biopsy analysis, only 9 of 20 metastatic lesions (45%) were pigmented with high melanin content. (123)I-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 melanin-negative lesions. The sensitivity and specificity of (123)I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively. Because of a low (123)I-BZA2 sensitivity, this clinical trial was prematurely closed after 87 patients had been included.
  
  
  CONCLUSIONS
  This study confirms the value of (18)F-FDG PET/CT for melanoma staging and strengthens the high accuracy of (123)I-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.
authors.affiliation: Nuclear Medicine, Jean Perrin Cancer Center, Clermont-Ferrand, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Cachin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gillet
authors.forename: Vanina
authors.initials: V
authors.lastname: Isnardi
authors.forename: Bruno
authors.initials: B
authors.lastname: Labeille
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meyer
authors.forename: Serge
authors.initials: S
authors.lastname: Cammilleri
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaudy
authors.forename: Micheline
authors.initials: M
authors.lastname: Razzouk-Cadet
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Lacour
authors.forename: Florence
authors.initials: F
authors.lastname: Granel-Brocard
authors.forename: Christelle
authors.initials: C
authors.lastname: Tychyj
authors.forename: Fathalah
authors.initials: F
authors.lastname: Benbouzid
authors.forename: Jean Daniel
authors.initials: JD
authors.lastname: Grange
authors.forename: Françoise
authors.initials: F
authors.lastname: Baulieu
authors.forename: Antony
authors.initials: A
authors.lastname: Kelly
authors.forename: Charles
authors.initials: C
authors.lastname: Merlin
authors.forename: Danielle
authors.initials: D
authors.lastname: Mestas
authors.forename: Françoise
authors.initials: F
authors.lastname: Gachon
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Françoise
authors.initials: F
authors.lastname: Degoul
authors.forename: Michel
authors.initials: M
authors.lastname: D'Incan
mesh_terms: D000368:Aged; D001549:Benzamides; D001706:Biopsy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008297:Male; D008543:Melanins / Q000096:biosynthesis / Q000737:chemistry*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000473:pathology*; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D008543:Melanins; C475761:N-(2-(diethylamino)ethyl)-2-iodobenzamide; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 131I BZA2; 18FDG; benzamide; melanin; melanoma staging