Biodistribution and clearance of small molecule hapten chelates for pretargeted radioimmunotherapy.
Biodistribution and clearance of small molecule hapten chelates for pretargeted radioimmunotherapy.
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DOI：
10.1007/s11307-010-0353-6
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发表时间：
2011-04
影响因子：
3.1
通讯作者：
Wittrup, K. Dane
中科院分区：
文献类型：
--
作者：
Orcutt, Kelly Davis;Nasr, Khaled A.;Whitehead, David G.;Frangioni, John V.;Wittrup, K. Dane
金属螯合1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）良好的药代动力学和临床安全性表明，它可能是一种理想的半抗原，用于预先靶向放射免疫治疗。为了尽量减少半抗原在正常组织中的滞留，并确定各种化学加合物对体内特性的影响，我们对一系列基于dota的衍生物进行了评估。研究了177lu标记的DOTA、DOTA生物素、双DOTA肽和DOTA氨基苯在正常CD1小鼠体内的生物分布和全身清除率。肾、肝和骨髓剂量使用标准医学内辐射剂量方法估计。所有半抗原均表现出类似的低组织和全身保留，注射后4小时小鼠体内仍保留注射剂量的2-4%。预计肾脏对所有177lu标记半抗原的剂量都有限制，估计肾脏剂量约为0.1 mGy/MBq。我们在此展示了一组基于dota的半抗原，它们在注射后4小时表现出快速清除和极低的全身潴留。氨基苯、酪氨酸-赖氨酸和生物素组对177Lu-DOTA的血液清除率和生物分布影响很小。
The favorable pharmacokinetics and clinical safety profile of metal-chelated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suggests that it might be an ideal hapten for pretargeted radioimmunotherapy. In an effort to minimize hapten retention in normal tissues and determine the effect of various chemical adducts on in vivo properties, a series of DOTA-based derivatives were evaluated. Biodistribution and whole-body clearance were evaluated for 177Lu-labeled DOTA, DOTA-biotin, a di-DOTA peptide, and DOTA-aminobenzene in normal CD1 mice. Kidney, liver, and bone marrow doses were estimated using standard Medical Internal Radiation Dose methodology. All haptens demonstrated similar low tissue and whole-body retention, with 2–4% of the injected dose remaining in mice 4 h postinjection. The kidney is predicted to be dose limiting for all 177Lu-labeled haptens tested with an estimated kidney dose of approximately 0.1 mGy/MBq. We present here a group of DOTA-based haptens that exhibit rapid clearance and exceptionally low whole-body retention 4 h postinjection. Aminobenzene, tyrosine–lysine, and biotin groups have minimal effects on the blood clearance and biodistribution of 177Lu-DOTA.
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影响因子：
9.3
作者：
Fisher, Darrell R.;Shen, Sui;Meredith, Ruby F.
通讯作者：
Meredith, Ruby F.
影响因子：
4.8
作者：
Chen, XY;Sievers, E;Conti, PS
通讯作者：
Conti, PS
DOI：
10.1016/j.ijrobp.2005.11.036
发表时间：
2006-04-01
影响因子：
7
作者：
Jaggi, JS;Seshan, SV;Scheinberg, DA
通讯作者：
Scheinberg, DA
影响因子：
--
作者：
Humblet, Valerie;Misra, Preeti;Frangioni, John V.
通讯作者：
Frangioni, John V.
影响因子：
6.7
作者：
Bourrinet, Philippe;Martel, Eric;Gaillard, Sophie
通讯作者：
Gaillard, Sophie