Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution.
Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution.
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DOI：
10.1111/j.1755-148x.2010.00716.x
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发表时间：
2010-10-01
影响因子：
4.3
通讯作者：
Moins, N
中科院分区：
文献类型：
--
作者：
Bonnet, M;Mishellany, F;Moins, N
靶向内放射性核素治疗（TRT）可能是一种有效的、特异性的治疗播散性黑色素瘤的方法。基于先前的药物调节研究，我们选择了一个喹诺啉衍生的分子（ICF01012），因为它具有黑色素特异性和适合TRT的动力学性质。在这里，我们通过人类黑色素瘤模型确定了[(131)I]ICF01012放射治疗在体外和体内与黑色素形成的关系。[(125)]ICF01012的摄取首先与黑色素含量有关。我们发现黑色素在不同模型中的分布代表了人类肿瘤的病理特征：黑色素在SKMel3肿瘤的细胞外空间中含量很高，而在M4Beu肿瘤中主要积聚在黑色素噬细胞中。靶向[(131)I]ICF01012放疗在色素肿瘤和非色素肿瘤中具有很强的抗肿瘤疗效，无论靶点分布和含量如何。该研究支持使用（131）i标记的碘喹诺啉靶向黑色素治疗黑色素瘤的有效治疗。
Targeted internal radionuclide therapy (TRT) could be an efficient, specific way to treat disseminated melanoma. Based on a previous pharmacomodulation study, we selected a quinoxaline-derived molecule (ICF01012) for its melanin specificity and kinetic properties suitable for TRT. Here, we determined the efficacy of [(131)I]ICF01012 radiotherapy in vitro and in vivo in relation to melanogenesis using human melanoma models. [(125)I]ICF01012 uptake was first assessed in relation to melanin content. We found that melanin distribution in different models was representative of pathology seen in human tumours: melanin content was high in the extracellular space of SKMel3 tumours, and accumulated primarily in melanophages in M4Beu tumours. Targeted [(131)I]ICF01012 radiotherapy had a strong anti-tumoural efficacy in pigmented versus unpigmented tumours, regardless of target distribution and content. This study supports the use of melanin targeting with (131)I-labelled iodoquinoxaline for effective treatment of melanoma.