Imaging cancer using PET--the effect of the bifunctional chelator on the biodistribution of a (64)Cu-labeled antibody.
Imaging cancer using PET--the effect of the bifunctional chelator on the biodistribution of a (64)Cu-labeled antibody.
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DOI：
10.1016/j.nucmedbio.2010.07.003
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发表时间：
2011-01
影响因子：
3.1
通讯作者：
Packard AB
中科院分区：
文献类型：
--
作者：
Dearling JL;Voss SD;Dunning P;Snay E;Fahey F;Smith SV;Huston JS;Meares CF;Treves ST;Packard AB
据报道，用于标记蛋白质的双功能螯合剂中的放射性核素丢失，因此在抗体放射性标记中使用铜放射性同位素受到了挑战。本研究的目的是研究五种常用双功能螯合剂 (BFC) 的 64Cu 复合物的热力学稳定性与使用这些螯合剂标记的 64Cu 抗体在荷瘤小鼠体内的生物分布之间的关系。将螯合剂（p-NH2-Bn-NOTA、BAT-6、p-NH2-Bn-DOTA、DOTA 和 SarAr）与抗 GD2 抗体 ch14.18 缀合，并将缀合抗体用 64Cu 标记并注射到带有皮下人类黑色素瘤肿瘤 (M21) 的小鼠中（每项研究 n = 3-5）。从注射后 1、24 和 48 小时采集的 PET 图像获得生物分布数据，并在注射后 48 小时进行完整的离体生物分布研究。所有放射免疫缀合物的生物分布（包括肿瘤靶向）相似。注射后 48 小时，放射性核素摄取的唯一统计学显着差异 (p < 0.05) 存在于血液、肝脏、脾脏和肾脏之间。例如，[64Cu]ch14.18-p-NH2-Bn-NOTA 的肝脏摄取量为每克组织注射剂量的 4.74 ± 0.77% (%ID/g)，[64Cu]ch14.18-SarAr 的摄取量为 8.06 ± 0.77%ID/g。肿瘤靶向的差异与肿瘤大小的变化相关，而不是与使用哪种 BFC 相关。这项研究的结果表明，这些螯合剂-Cu(II) 配合物的热力学稳定性差异与肿瘤对示踪剂的摄取的显着差异无关。然而，其他组织中的示踪剂浓度存在显着差异，包括那些涉及放射免疫缀合物清除的组织（例如肝脏和脾脏）。
Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the 64Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with 64Cu using these chelators in tumor-bearing mice. The chelators (p-NH2-Bn-NOTA, BAT-6, p-NH2-Bn-DOTA, DOTA, and SarAr) were conjugated to the anti-GD2 antibody ch14.18, and the conjugated antibody was labeled with 64Cu and injected into mice bearing subcutaneous human melanoma tumors (M21) (n = 3-5 for each study). Biodistribution data were obtained from PET images acquired at 1, 24 and 48 hours post-injection, and at 48 hours post-injection a full ex vivo biodistribution study was carried out. The biodistribution, including tumor targeting, was similar for all the radioimmunoconjugates. At 48 h post-injection, the only statistically significant differences in radionuclide uptake (p < 0.05) were between blood, liver, spleen and kidney. For example, liver uptake of [64Cu]ch14.18-p-NH2-Bn-NOTA was 4.74 ± 0.77 per cent of the injected dose per gram of tissue (%ID/g), and for [64Cu]ch14.18-SarAr was 8.06 ± 0.77 %ID/g. Differences in tumor targeting correlated with variations in tumor size rather than which BFC was used. The results of this study indicate that differences in the thermodynamic stability of these chelator-Cu(II) complexes were not associated with significant differences in uptake of the tracer by the tumor. However, there were significant differences in tracer concentration in other tissues, including those involved in clearance of the radioimmunoconjugate (e.g., liver and spleen).
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影响因子：
2.9
作者：
MOI, MK;MEARES, CF;DENARDO, SJ
通讯作者：
DENARDO, SJ
影响因子：
4.6
作者：
BEVILACQUA, A;GELB, RI;ZOMPA, LJ
通讯作者：
ZOMPA, LJ
DOI：
10.1039/b103242a
发表时间：
2001-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS
影响因子：
--
作者：
Di Bartolo, NM;Sargeson, AM;Smith, SV
通讯作者：
Smith, SV
影响因子：
6.2
作者：
SHARMA, SK;BAGSHAWE, KD;SHERWOOD, RF
通讯作者：
SHERWOOD, RF
影响因子：
2.9
作者：
MEARES, CF;MCCALL, MJ;MCTIGUE, M
通讯作者：
MCTIGUE, M