Preclinical Evaluation of an 131I-Labeled Benzamide for Targeted Radiotherapy of Metastatic Melanoma

Joyal, John L.; Barrett, John; Marquis, John; Chen, Jianqing; Hillier, Shawn; Maresca, Kevin P.; Boyd, Marie; Gage, Kenneth L.; Nimmagadda, Sridhar; Kronauge, James F.; Friebe, Matthias; Dinkelborg, Ludger; Stubbs, James B.; Stabin, Michael G.; Mairs, Robert J.; Pomper, Martin G.; Babich, John W.

doi:10.1158/0008-5472.can-09-4414

Cited by 47 publications

(47 citation statements)

References 39 publications

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“…The higher sensitivity of PET and SPECT in many malignancies is noteworthy. 18 F-FDG is one of the most widely used clinical PET radiopharmaceuticals. It has proven useful in the Hongyan Feng and Xiaotian Xia contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

“…Several radiopharmaceuticals have been developed to bind to melanoma and localize metastatic melanoma lesions, including radiolabelled monoclonal antibodies [10,11], peptides (melanocortin type 1 receptor, MC1R) [12][13][14], iodoamphetamine [15,16], benzamide (BZA) [17][18][19], and BZA analogues [20][21][22][23][24]. Monoclonal antibodies labelled with different radioisotopes against melanoma-associated antigens (MAA), and labelled α-melanocyte-stimulating hormone (α-MSH) or α-MSH analogues binding to MC1R, have shown some potential in diagnosis and radioimmunotherapy [10,14].…”

Section: Introductionmentioning

confidence: 99%

“…The synthesis of an α-MSH analogue, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH 2 (NAPamide) and the preparation of 18 F-radiolabelled NAPamide ( 18 F-FB-NAPamide) have been reported [13]. The retention time of 18 F-FB-NAPamide in melanoma lesions is short. The uptake value in B16F10 tumours is 1.19 ± 0.11 %ID/g at 1 h, and the activity decreases to 0.25 ± 0.05 %ID/g at 4 h after injection [13].…”

Section: Introductionmentioning

confidence: 99%

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Imaging malignant melanoma with 18F-5-FPN

Feng

Xia

et al. 2015

Eur J Nucl Med Mol Imaging

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Imaging malignant melanoma with 18F-5-FPN

Feng

Xia

et al. 2015

Eur J Nucl Med Mol Imaging

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“…[11][12][13][14][15] With these agents the radionuclide ( 11 C, 125 I, 18 F) is attached to the cysteine or lysine moiety via a small prosthetic group. For large molecular fragments, such as radiometal ( 99m Tc, 68 Ga) chelators, organic fluorescent molecules, and nanoparticles, we have determined that a linking moiety of at least 20Å between the large molecule and the lysine moiety is needed.…”

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confidence: 99%

Sequential SPECT and Optical Imaging of Experimental Models of Prostate Cancer with a Dual Modality Inhibitor of the Prostate‐Specific Membrane Antigen

et al. 2011

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“…Melanin-targeted imaging could be the first step in selecting patients with pigmented metastases, allowing them to become candidates for targeted therapy. Along with others (26,27), we are developing melanin-targeted radiopharmaceuticals dedicated to melanoma treatment based on a quinoxaline derivative, ICF01012, which in preclinical models has demonstrated promising antitumoral activity after labeling with 131 I (28). This tracer was recently selected for a first-in-human clinical trial to determine tolerance, distribution, and dosimetry in patients with metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

¹²³I-BZA2 as a Melanin-Targeted Radiotracer for the Identification of Melanoma Metastases: Results and Perspectives of a Multicenter Phase III Clinical Trial

et al. 2013

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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 melaninnegative 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. Conclusion: 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. Mel anoma accounts for nearly 80% of all deaths related to cutaneous cancer (1). It is the second most common cancer among patients in their second decade (2). For localized lesions with a tumor thickness of less than 1.5 mm (stage I or II), melanoma can be cured by tota...

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Preclinical Evaluation of an 131I-Labeled Benzamide for Targeted Radiotherapy of Metastatic Melanoma

Cited by 47 publications

References 39 publications

Imaging malignant melanoma with 18F-5-FPN

Imaging malignant melanoma with 18F-5-FPN

Sequential SPECT and Optical Imaging of Experimental Models of Prostate Cancer with a Dual Modality Inhibitor of the Prostate‐Specific Membrane Antigen

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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Preclinical Evaluation of an 131I-Labeled Benzamide for Targeted Radiotherapy of Metastatic Melanoma

Cited by 47 publications

References 39 publications

Imaging malignant melanoma with 18F-5-FPN

Imaging malignant melanoma with 18F-5-FPN

Sequential SPECT and Optical Imaging of Experimental Models of Prostate Cancer with a Dual Modality Inhibitor of the Prostate‐Specific Membrane Antigen

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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¹²³I-BZA2 as a Melanin-Targeted Radiotracer for the Identification of Melanoma Metastases: Results and Perspectives of a Multicenter Phase III Clinical Trial