Linked Life Data

20941431

Source:http://linkedlifedata.com/resource/pubmed/id/20941431

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2010-11-25
pubmed:abstractText
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 (64)Cu(2+). 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 (64)Cu(2+) (<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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1473-0197
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3387-96
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Microfluidic labeling of biomolecules with radiometals for use in nuclear medicine.
pubmed:affiliation
Institute for Genomic Biology, University of Illinois at Urbana Champaign, 1206 W. Gregory Dr., Urbana, IL 61801, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural