2-Mercaptoacetylglycylglycyl (MAG2) as a bifunctional chelator for 99mTc-labeling of cyclic RGD dimers: effect of technetium chelate on tumor uptake and pharmacokinetics.
2-Mercaptoacetylglycylglycyl (MAG2) as a bifunctional chelator for 99mTc-labeling of cyclic RGD dimers: effect of technetium chelate on tumor uptake and pharmacokinetics.
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DOI：
10.1021/bc9001739
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发表时间：
2009-08-19
影响因子：
4.7
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Shi J;Kim YS;Chakraborty S;Jia B;Wang F;Liu S
本报告描述了MAG 2-PEG 4-E[c（RGDfK）]2的合成（MAG 2-P-RGD 2：MAG 2 = S-苯甲酰基巯基乙酰基甘氨酰基甘氨酰基; PEG 4 = 15-氨基-4，7，10，13-四氧杂十五烷酸）和MAG 2-PEG 4-E[PEG 4-c（RGDfK）]2（MAG 2 - 3 P-RGD 2），以及评价99 mTcO（MAG 2-P-RGD 2）和99 mTcO（MAG 2 - 3 P-RGD 2）作为携带U87 MG人胶质瘤异种移植物的无胸腺裸鼠中肿瘤成像的新放射性示踪剂。我们发现MAG 2是一种高效的双功能螯合剂，使用试剂盒配方可以以高收率（>90%）制备99 mTcO（MAG 2-P-RGD 2）和99 mTcO（MAG 2 - 3 P-RGD 2），并且具有高比活度（<15 Ci/μmol）。99 mTcO（MAG 2-P-RGD 2）和99 mTcO（MAG 2 - 3 P-RGD 2）在试剂盒基质中具有非常高的溶液稳定性。在荷U87 MG人胶质瘤异种移植物的无胸腺裸鼠中的生物分布数据表明，替换高电荷的[99 mTc（HYNIC）（tricine）（TPPTS）]（6-肼基烟基和TPPTS =三苯基膦-3，3 ′三钠，3″-三磺酸盐）与较小的99 mTcO（MAG 2）一起导致肿瘤和正常器官中放射性示踪剂摄取的显著增加，这很可能是由于99 mTcO的亲脂性较高（MAG2-3P-RGD2）（log P = -3.15 ± 0.10）比[99mTc（HYNIC-3P-RGD2）（tricine）（TPPTS）]（99mTc-3P-RGD2：log P = -3.96 ± 0.05）更高。尽管99 mTcO（MAG 2 - 3 P-RGD 2）具有更好的肿瘤摄取（在注射后（p.i.）比99mTc-3P-RGD2（9.15 ± 2.13% ID/g，60 min p.i.），其肿瘤与背景（T/B）比值（肿瘤/血液= 13.02 ± 6.12;肿瘤/肝脏= 4.07 ± 0.95;肿瘤/肺= 2.97 ± 0.64;肿瘤/肌肉= 8.04 ± 0.43）的放射性活度均低于99 mTc-3 P-RGD 2（肿瘤/血液= 36.0 ± 11.5;肿瘤/肝= 5.14 ± 1.46;肿瘤/肺= 4.36 ± 0.54;和肿瘤/肌肉= 13.70 ± 2.21）。基于这些结果，我们认为99 mTc-3 P-RGD 2仍然是一个更好的放射性示踪剂，因为它具有更高的T/B比值。
This report describes the synthesis of MAG2-PEG4-E[c(RGDfK)]2 (MAG2-P-RGD2: MAG2 = S-benzoylmercaptoacetylglycylglycyl; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and MAG2-PEG4-E[PEG4-c(RGDfK)]2 (MAG2-3P-RGD2), and the evaluation of 99mTcO(MAG2-P-RGD2) and 99mTcO(MAG2-3P-RGD2) as new radiotracers for tumor imaging in the athymic nude mice bearing U87MG human glioma xenografts. We found that MAG2 is such an efficient bifunctional chelating agent that 99mTcO(MAG2-P-RGD2) and 99mTcO(MAG2-3P-RGD2) could be prepared in high yield (>90%) with high specific activity (∼5 Ci/μmol) using a kit formulation. 99mTcO(MAG2-P-RGD2) and 99mTcO(MAG2-3P-RGD2) have very high solution stability in the kit matrix. Biodistribution data in athymic nude mice bearing U87MG human glioma xenografts indicated that replacing the highly charged [99mTc(HYNIC)(tricine)(TPPTS)] (6-hydrazinonicotinyl and TPPTS = trisodium triphenylphosphine-3,3′,3″-trisulfonate) with smaller 99mTcO(MAG2) resulted in a significant increase in the radiotracer uptake in the tumor and normal organs most likely due to the higher lipophilicity of 99mTcO(MAG2-3P-RGD2) (log P = -3.15 ± 0.10) than that for [99mTc(HYNIC-3P-RGD2)(tricine)(TPPTS)] (99mTc-3P-RGD2: log P = -3.96 ± 0.05). Even though 99mTcO(MAG2-3P-RGD2) has better tumor uptake (15.48 ± 2.49 %ID/g at 60 min postinjection (p.i.)) than 99mTc-3P-RGD2 (9.15 ± 2.13 %ID/g at 60 min p.i.), its tumor-to-background (T/B) ratios (tumor/blood = 13.02 ± 6.12; tumor/liver = 4.07 ± 0.95; tumor/lung = 2.97 ± 0.64; and tumor/muscle = 8.04 ± 0.43) are not as good as those of 99mTc-3P-RGD2 (tumor/blood = 36.0 ± 11.5; tumor/liver = 5.14 ± 1.46; tumor/lung = 4.36 ± 0.54; and tumor/muscle = 13.70 ± 2.21) at 60 min p.i. On the basis of these results, we believe that 99mTc-3P-RGD2 remains a better radiotracer because of its higher T/B ratios.
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影响因子：
3.1
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