Microfluidic radiolabeling of biomolecules with PET radiometals.
Microfluidic radiolabeling of biomolecules with PET radiometals.
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DOI：
10.1016/j.nucmedbio.2012.08.012
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发表时间：
2013-01
影响因子：
3.1
通讯作者：
Reichert DE
中科院分区：
文献类型：
--
作者：
Zeng D;Desai AV;Ranganathan D;Wheeler TD;Kenis PJ;Reichert DE
设计、制造和测试了一种坚固、多功能和紧凑的微反应器，用于标记双功能螯合共轭生物分子(BFC-BM)和PET放射性金属。用所研制的微反装置对1，4，7，10-Tetraazacyclododecane-1，4，7，10-tetraacetic酸和1，4，7-三氮杂环-1，4，7-三乙酸三乙酸酯分别与64Cu和68Ga的环状多肽进行了放射性标记。通过改变温度、浓度和停留时间，优化了微反应器的标记条件。微反应器方法与传统方法的直接比较表明，由于微尺度上的质量和热传递增强，在相同的标记条件下，微反应器的标记率和重现性都得到了提高。更重要的是，通过微反应器中双功能螯合生物分子偶合物(BFC-BM)与放射性金属的1：1化学计量比，获得了超过90%的放射性标记产率(掺入放射性金属)，这潜在地避免了广泛的层析纯化，这通常需要去除用传统方法制备的放射性配体中大量过量的未标记生物分子。此外，用64Cu/68Ga标记DOTA功能化的BSA蛋白(牛血清白蛋白)的产率较高，这表明它既可以标记小分子，也可以标记大分子。开发并验证了一种坚固、可靠、紧凑的微反应器，它能够将放射性金属与常见的螯合物进行螯合。根据我们的放射性标记结果，报道的微流控方法总体上优于传统的放射性合成方法，是一种很有前途的水溶液中常用的BFC-BM的放射性金属标记技术。
A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64Cu and 68Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64Cu/68Ga using the microreactor, which demonstrates the ability to label both small and large molecules. A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.
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DOI：
10.2967/jnumed.109.065946
发表时间：
2010-02
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Elizarov AM;van Dam RM;Shin YS;Kolb HC;Padgett HC;Stout D;Shu J;Huang J;Daridon A;Heath JR
通讯作者：
Heath JR
影响因子：
16.6
作者：
Audrain, Helen
通讯作者：
Audrain, Helen
影响因子：
3.1
作者：
McCarthy, DW;Bass, LA;Welch, MJ
通讯作者：
Welch, MJ
影响因子：
6.1
作者：
Lu, SY;Watts, P;Pike, VW
通讯作者：
Pike, VW
影响因子：
4.6
作者：
Reichert, DE;Hancock, RD;Welch, MJ
通讯作者：
Welch, MJ