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Issue 24, 2010
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Microfluidic labeling of biomolecules with radiometals for use in nuclear medicine

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Radiometal-based radiopharmaceuticals, used as imaging and therapeutic agents in nuclear medicine, consist of a radiometal that is bound to a targeting biomolecule (BM) using a bifunctional chelator (BFC). Conventional, macroscale radiolabeling methods use an excess of the BFC–BM conjugate (ligand) to achieve high radiolabeling yields. Subsequently, to achieve maximal specific activity (minimal amount of unlabeled ligand), extensive chromatographic purification is required to remove unlabeled ligand, often resulting in longer synthesis times and loss of imaging sensitivity due to radioactive decay. Here we describe a microreactor that overcomes the above issues through integration of efficient mixing and heating strategies while working with small volumes of concentrated reagents. As a model reaction, we radiolabel 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated to the peptide cyclo(Arg-Gly-Asp-DPhe-Lys) with 64Cu2+. We show that the microreactor (made from polydimethylsiloxane and glass) can withstand 260 mCi of activity over 720 hours and retains only minimal amounts of 64Cu2+ (<5%) upon repeated use. A direct comparison between the radiolabeling yields obtained using the microreactor and conventional radiolabeling methods shows that improved mixing and heat transfer in the microreactor leads to higher yields for identical reaction conditions. Most importantly, by using small volumes (∼10 µL) of concentrated solutions of reagents (>50 µM), yields of over 90% can be achieved in the microreactor when using a 1 : 1 stoichiometry of radiometal to BFC–BM. These high yields eliminate the need for use of excess amounts of often precious BM and obviate the need for a chromatographic purification process to remove unlabeled ligand. The results reported here demonstrate the potential of microreactor technology to improve the production of patient-tailored doses of radiometal-based radiopharmaceuticals in the clinic.

Graphical abstract: Microfluidic labeling of biomolecules with radiometals for use in nuclear medicine

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Publication details

The article was received on 01 Jul 2010, accepted on 10 Sep 2010 and first published on 12 Oct 2010

Article type: Paper
DOI: 10.1039/C0LC00162G
Citation: Lab Chip, 2010,10, 3387-3396
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    Microfluidic labeling of biomolecules with radiometals for use in nuclear medicine

    T. D. Wheeler, D. Zeng, A. V. Desai, B. Önal, D. E. Reichert and P. J. A. Kenis, Lab Chip, 2010, 10, 3387
    DOI: 10.1039/C0LC00162G

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