Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging.
Synthesis of fluorine-18 radio-labeled serum albumins for PET blood pool imaging.
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DOI：
10.1016/j.nucmedbio.2014.11.011
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Jagoda EM
中科院分区：
文献类型：
--
作者：
Basuli F;Li C;Xu B;Williams M;Wong K;Coble VL;Vasalatiy O;Seidel J;Green MV;Griffiths GL;Choyke PL;Jagoda EM
我们试图开发一种用氟-18放射性标记血清白蛋白的实用的、可重复的和临床上可转化的方法，以用作动物和人的PET血池成像剂。氟-18放射性标记的氟烟酸-2，3，5，6-四氟苯基酯，[18 F]F-Py-TFP首先通过其季铵三氟甲磺酸盐前体与[18 F]四丁基氟化铵反应来制备（[18F]TBAF），具有微小的修改。将[18F]F-Py-TFP与大鼠血清白蛋白（RSA）在磷酸盐缓冲液（pH 9）中于37-40 ℃孵育15 min，产生氟-18-放射性标记的RSA，并使用mini-PD MiniTrap G-25柱纯化产物。在90分钟合成中，反应的总放射化学产率为18-35%（n = 30，未校正）。用人血清白蛋白（HSA）重复该程序，得到类似的结果。氟-18-放射性标记的RSA在健康清醒大鼠中表现出延长的血液潴留（生物半衰期为4.8小时）。在4小时观察期间，通过直接组织计数或动态PET全身成像，主要器官放射性的分布保持相对不变，但标记代谢产物在膀胱中逐渐蓄积除外。这种用于合成放射性标记的血清白蛋白的手动方法使用氟-18（一种广泛可用的PET放射性核素）和纯的和重组形式的天然蛋白质，其可以按比例放大用于广泛的临床应用。这些临床前生物分布和PET成像结果表明，[18 F]RSA是一种有效的大鼠血池成像剂，并且可能与[18 F]HSA一样，证明类似地可用作临床成像剂。
We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [18F]tetrabutylammonium fluoride ([18F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [18F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 min at 37–40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18–35% (n = 30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [18F]RSA is an effective blood pool imaging agent in rats and might, as [18F]HSA, prove similarly useful as a clinical imaging agent.
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影响因子：
1.6
作者：
GUHLKE, S;COENEN, HH;STOCKLIN, G
通讯作者：
STOCKLIN, G
影响因子：
7.3
作者：
Olberg, Dag E.;Arukwe, Joseph M.;Cuthbertson, Alan
通讯作者：
Cuthbertson, Alan
影响因子：
1
作者：
Ramenda, Theres;Bergmann, Ralf;Wuest, Frank
通讯作者：
Wuest, Frank
影响因子：
4.7
作者：
GARG, PK;GARG, S;ZALUTSKY, MR
通讯作者：
ZALUTSKY, MR
影响因子：
5.8
作者：
Saatchi, Katayoun;Gelder, Nikolaus;Haefeli, Urs O.
通讯作者：
Haefeli, Urs O.