Synthesis and Evaluation of Novel Radioiodinated Benzamides for Malignant Melanoma

Pham, Tien; Greguric, Ivan; Liu, Xiang; Berghofer, Paula; Ballantyne, Patrice; Chapman, J.F.; Mattner, Filomena; Dikic, Branko; Jackson, Timothy; Loc'h, and Christian; Katsifis, Andrew

doi:10.1021/jm0701627

Cited by 40 publications

(45 citation statements)

References 22 publications

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“…In recent years, several other radiolabeled imaging probes have been evaluated for melanoma imaging, including methylene blue dye (10), monoclonal antibodies against melanoma-associated antigens (11,12), iodoamphetamine (13), a-melanocyte-stimulating hormone ana-logs (14,15), and benzamide (BZA)-based compounds (16,17). To date, iodinated BZA analogs have been among the most promising of the newer melanoma radiotracers for both diagnosis and therapeutic applications.…”

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confidence: 99%

High-Contrast PET of Melanoma Using ¹⁸F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance

Denoyer¹,

Greguric²,

Roselt³

et al. 2010

J Nucl Med

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The aim of this study was to evaluate the novel probe 18 F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide ( 18 F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using 18 F-MEL050 was performed in murine models of melanoma. The specificity of 18 F-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. 18 F-MEL050 PET results were compared with 18 F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of 18 F-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, 18 F-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 18 F-MEL050 than for 18 F-FDG (50.9 6 6.9 vs. 5.8 6 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of 18 F-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 18 F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: 18 F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.

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confidence: 99%

High-Contrast PET of Melanoma Using ¹⁸F-MEL050, a Selective Probe for Melanin with Predominantly Renal Clearance

Denoyer¹,

Greguric²,

Roselt³

et al. 2010

J Nucl Med

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“…This further validated the potential of these types of compounds for therapeutic applications of metastatic melanoma and hence led our research group to the development of [ 123 I]MEL037 (5, Figure 1), which demonstrated high and prolonged tumor uptake, rapid whole body clearance, and potential therapeutic application. 25 The structural modifications undertaken for 5 included a benzyl substituent (for straightforward radiolabeling via the stannyl precursor), the incorporation of stable functional groups (piperazine center) 26 into the amide, as well as the replacement of the benzamide/nicotinamide with an isoindolin-1,3-dione (phthalimide) to produce a more rigid and in vivo stable molecule. 27 Studies demonstrated 5 to have a 3-fold higher tumor uptake than 2, with rapid whole body clearance; 27 however, further preclinical evaluation of [ 131 I]5 found the compound did not show the longitudinal in vivo stability required to be a suitable therapeutic agent.…”

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confidence: 99%

Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

et al. 2015

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This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [(123)I]4 (ICF01012). The most favorable compounds ([(123)I]20, [(123)I]23, [(123)I]41, and [(123)I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [(123)I]20 and [(123)I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [(123)I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [(123)I]41 and [(123)I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [(123)I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [(131)I] therapeutic evaluation.

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“…For several years, a series of radioiodinated benzamide derivatives described to selectively concentrate into melanin rich cells, in particular melanoma cells have been developed as radiopharmaceuticals [4][5][6][7][8][9][10]. One of them, N-(2-diethylaminoethyl)-4-iodobenzamide ([ 123 I]BZA, Fig.…”

Section: Introductionmentioning

confidence: 99%

Development of a high-performance liquid chromatographic method for the determination of a new potent radioiodinated melanoma imaging and therapeutic agent

Denoyer

Labarre

Papon

et al. 2008

Journal of Chromatography B

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Synthesis and Evaluation of Novel Radioiodinated Benzamides for Malignant Melanoma

Cited by 40 publications

References 22 publications

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

Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents

Development of a high-performance liquid chromatographic method for the determination of a new potent radioiodinated melanoma imaging and therapeutic agent

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Synthesis and Evaluation of Novel Radioiodinated Benzamides for Malignant Melanoma

Cited by 40 publications

References 22 publications

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

Synthesis and in Vivo Evaluation of [123I]Melanin-Targeted Agents

Development of a high-performance liquid chromatographic method for the determination of a new potent radioiodinated melanoma imaging and therapeutic agent

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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

Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents