Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy.
Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy.
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DOI：
10.1016/j.neo.2016.11.001
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发表时间：
2017-01
期刊：
影响因子：
4.8
通讯作者：
Miot-Noirault, Elisabeth
中科院分区：
文献类型：
--
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
目得：这项工作报告，在黑色素瘤模型，治疗诊断潜力的ICF 15002作为一个单一的氟化和碘化黑色素靶向化合物。方法：在小鼠同基因B16 BL 6模型和A375和SK-MEL-3人异种移植物中进行研究。用氟-18对ICF 15002进行放射性标记，用于正电子发射断层扫描（PET）成像和生物分布，用碘-125进行代谢研究，用碘-131进行靶向放射性核素治疗（TRT）。通过肿瘤体积测量评估TRT疗效，并在B16 BL 6模型中确定机械学和剂量学参数。ICF 15002的细胞内定位通过二次离子质谱（西姆斯）表征。研究结果：用[18F] ICF 15002进行的PET成像证明，在接种后1小时，着色的B16 BL 6和SK-MEL-3模型中的肿瘤摄取分别为14.33 ± 2.11%ID/g和4.87 ± 0.93%ID/g。在无色素A375黑色素瘤中未观察到蓄积。西姆斯证实了在B16 BL 6肿瘤的黑素体中，ICF 15002信号与黑素聚合物共定位。TRT联合2个剂量的20 MBq [131 I] ICF 15002向B16 BL 6肿瘤输送的吸收剂量为102.3戈伊，导致显著的肿瘤生长抑制[治疗组倍增时间（DT）为2.9 ± 0.5天，对照组为1.8 ± 0.3天]和中位生存期延长（27天，对照组为21天）。P53 S15磷酸化和P21诱导与G2/M阻滞相关，提示有丝分裂灾难。在人SK-MEL-3模型中，25 MBq的三个剂量也导致DT增加（26.5 ± 7.8天vs对照组11.0 ± 3.8天）和中位生存期改善（111天vs对照组74天）。结论：结果表明，ICF 15002具有适用于色素性黑色素瘤患者的双峰成像/TRT管理的特性。
PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET) imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT). TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS). RESULTS: PET imaging with [18F]ICF15002 evidenced tumoral uptake of 14.33 ± 2.11%ID/g and 4.87 ± 0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [131I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT) of 2.9 ± 0.5 days in treated vs 1.8 ± 0.3 in controls] and a prolonged median survival (27 days vs 21 in controls). P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5 ± 7.8 days vs 11.0 ± 3.8 in controls) and improved median survival (111 days vs 74 in controls). CONCLUSION: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma.
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DOI：
10.1007/s00259-012-2168-y
发表时间：
2012-09-01
影响因子：
9.1
作者：
Rbah-Vidal, Latifa;Vidal, Aurelien;Chezal, Jean-Michel
通讯作者：
Chezal, Jean-Michel
影响因子：
4.3
作者：
Bonnet, M;Mishellany, F;Moins, N
通讯作者：
Moins, N
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：
7.3
作者：
Eisenhut, M;Hull, WE;Haberkorn, U
通讯作者：
Haberkorn, U
影响因子：
6.7
作者：
Maisonial, Aurelie;Billaud, Emilie M. F.;Chezal, Jean-Michel
通讯作者：
Chezal, Jean-Michel