Synthesis and characterization of a novel radioiodinated phenylacetamide and its homolog as theranostic agents for malignant melanoma

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• 作者：Chih-Chao Chang^a ; Chih-Hsien Chang^a ; ^b ; Chih-Chieh Shen^c ; Chuan-Lin Chen^a ; Ren-Shyan Liu^a ; ^d ; ^e ; Ming-Hsien Lin^f ; ^{md317317@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Hsin-Ell Wang^a ; ^{hewang@ym.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Melanoma ; Melanin ; B16F0 ; SPECT ; Phenylacetamide ; Theranostic agents
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：81
• 期：Complete
• 页码：201-209
• 全文大小：851 K

文摘

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. This study reports the preparation and biological characterizations of N-(2-(diethylamino)ethyl)-2-(3-^123/131I-iodo-4-hydroxyphenyl)acetamide and N-(2-(diethylamino)ethyl)-3-(3-^123/131I-iodo-4-hydroxyphenyl)propanamide (^123/131I-IHPA and ^123/131I-IHPP) as novel melanin-specific theranostic agents. These two tracers were hydrophilic, exhibited good serum stability and high binding affinity to melanin. In vitro and in vivo studies revealed rapid, high and tenacious uptakes of both ¹³¹I-IHPA and ¹³¹I-IHPP in melanotic B16F0 cell line and in C57BL/6 mice bearing B16F0 melanoma, but not in amelanonic A375 cell line and tumors. Small-animal SPECT imaging also clearly delineate B16F0 melanoma since 1 h postinjection of ¹²³I-IHPA and ¹²³I-IHPP in tumor-bearing mice. Owing to the favorable biodistribution of ¹³¹I-IHPA and ¹³¹I-IHPP after intravenous administration, the estimated absorption dose was low in most normal organs and relatively high in melanotic tumor. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and acceptable projected human dosimetry supported that these two tracers are promising theranostic agents for melanin-positive melanoma.