Targeted radiotherapy of pigmented melanoma with 131I-5-IPN
Targeted radiotherapy of pigmented melanoma with 131I-5-IPN
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131I-5-IPN 靶向放射治疗色素性黑色素瘤
DOI：
10.1186/s13046-018-0983-0
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发表时间：
2018-12
影响因子：
11.3
通讯作者：
Xiaoli Lan
中科院分区：
文献类型：
--
作者：
Xiaodong Xu;Lujie Yuan;Yongkang Gai;Qingyao Liu;Lianglan Yin;Yaqun Jiang;Yichun Wang;Yongxue Zhang;Xiaoli Lan
到目前为止，还没有令人满意的治疗晚期黑色素瘤的方法。靶向放射性核素治疗（TRNT）可能是治疗这种迄今为止致命疾病的一个有希望的选择。本研究目的是合成131I-N-（2-（二乙基氨基）乙基）-5-（碘- 131i）picolinamide (131I-5-IPN)，并评价其作为放射性碘化黑色素靶向治疗剂的治疗能力和毒性。合成三甲基锡基前体并用131I标记得到131I-5- ipn。通过SPECT显像评估131I-5-IPN的药代动力学，并评估其在B16F10肿瘤模型和A375人鼠异种移植物中的生物分布。对于TRNT， B16F10黑色素瘤小鼠随机分为五组（每组n = 10）： A组（对照组）给予0.1 mL生理盐水；B组给予等摩尔剂量的未标记前体；C组给予18.5 MBq的[131I]NaI；D组和E组分别给予18.5 MBq 131I-5-IPN 1剂和2剂。通过肿瘤体积测量和生物学研究评价TRNT的疗效。131I-5-IPN对重要器官的毒性作用通过实验室试验和组织病理学检查进行评估。根据生物分布数据估计了重要器官的辐射吸收剂量。成功制备了131I-5-IPN，放射化学产率（55%±5%,n = 5），在黑色素阳性的B16F10细胞中具有较高的摄取率，特异性高。SPECT成像和131I-5-IPN的生物分布显示色素B16F10模型持续72小时的高肿瘤摄取。含有131I-5-IPN的TRNT具有显著的抗肿瘤作用，与a、B和c组相比，D组和E组的中位生存期延长。肝脏的最高吸收剂量为0.25 mSv/MBq；治疗过程中未见肝、肾明显损伤。131I-5-IPN治疗可降低肿瘤组织增殖细胞核抗原（PCNA）和Ki67的表达，阻断G2/M期细胞周期。TRNT后血管内皮生长因子和CD31表达降低，表明肿瘤生长减少。我们成功合成了131I-5-IPN，它在黑色素瘤中具有长时间的保留。TRNT联合131I-5-IPN有可能成为一种安全有效的治疗色素黑色素瘤的策略。
There has been no satisfactory treatment for advanced melanoma until now. Targeted radionuclide therapy (TRNT) may be a promising option for this heretofore lethal disease. Our goal in this study was to synthesize 131I-N-(2-(diethylamino)ethyl)-5-(iodo-131I)picolinamide (131I-5-IPN) and evaluate its therapeutic ability and toxicity as a radioiodinated melanin-targeting therapeutic agent. The trimethylstannyl precursor was synthesized and labeled with 131I to obtain 131I-5-IPN. The pharmacokinetics of 131I-5-IPN was evaluated through SPECT imaging, and its biodistribution was assessed in B16F10 tumor models and in A375 human-to-mouse xenografts. For TRNT, B16F10 melanoma-bearing mice were randomly allocated to receive one of five treatments (n = 10 per group): group A (the control group) received 0.1 mL saline; group B was treated with an equimolar dose of unlabeled precursor; group C received 18.5 MBq of [131I]NaI; group D and E received one or two dose of 18.5 MBq 131I-5-IPN, respectively. TRNT efficacy was evaluated through tumor volume measurement and biology study. The toxic effects of 131I-5-IPN on vital organs were assessed with laboratory tests and histopathological examination. The radiation absorbed dose to vital organs was estimated based on biodistribution data. 131I-5-IPN was successfully prepared with a good radiochemistry yield (55% ± 5%, n = 5), and it exhibited a high uptake ratio in melanin-positive B16F10 cells which indicating high specificity. SPECT imaging and biodistribution of 131I-5-IPN showed lasting high tumor uptake in pigmented B16F10 models for 72 h. TRNT with 131I-5-IPN led to a significant anti-tumor effect and Groups D and E displayed an extended median survival compared to groups A, B, and C. The highest absorbed dose to a vital organ was 0.25 mSv/MBq to the liver; no obvious injury to the liver or kidneys was observed during treatment. 131I-5-IPN treatment was associated with reduction of expression of proliferating cell nuclear antigen (PCNA) and Ki67 and cell cycle blockage in G2/M phase in tumor tissues. Decreased vascular endothelial growth factor and CD31 expression, implying reduced tumor growth, was noted after TRNT. We successfully synthesized 131I-5-IPN, which presents long-time retention in melanotic melanoma. TRNT with 131I-5-IPN has the potential to be a safe and effective strategy for management of pigmented melanoma.
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DOI：
10.1007/s002590050416
发表时间：
1999-04
期刊：
European Journal of Nuclear Medicine
影响因子：
--
作者：
P. Labarre;J. Papon;M. Moreau;N. Moins;A. Veyre;J. Madelmont
通讯作者：
P. Labarre;J. Papon;M. Moreau;N. Moins;A. Veyre;J. Madelmont
影响因子：
9.3
作者：
Cachin, Florent;Miot-Noirault, Elisabeth;D'Incan, Michel
通讯作者：
D'Incan, Michel
影响因子：
9.3
作者：
Denoyer, Delphine;Greguric, Ivan;Hicks, Rodney J.
通讯作者：
Hicks, Rodney J.
影响因子：
4.8
作者：
Rbah-Vidal, Latifa;Vidal, Aurelien;Billaud, Emilie M. F.;Besse, Sophie;Ranchon-Cole, Isabelle;Mishellany, Florence;Perrot, Yann;Maigne, Lydia;Moins, Nicole;Guerquin-Kern, Jean-Luc;Degoul, Francoise;Chezal, Jean-Michel;Auzeloux, Philippe;Miot-Noirault, Elisabeth
通讯作者：
Miot-Noirault, Elisabeth
用 PET 检测黑色素瘤转移——F-18-5-FPN 与 F-18-FDG 的比较
影响因子：
3.1
作者：
Wang Yichun;Li Mengting;Zhang Yingying;Zhang Fengzhen;Liu Chunbao;Song Yiling;Zhang Yongxue;Lan Xiaoli
通讯作者：
Lan Xiaoli