TY - JOUR
T1 - Microfluidic radiolabeling of biomolecules with PET radiometals
AU - Zeng, Dexing
AU - Desai, Amit V.
AU - Ranganathan, David
AU - Wheeler, Tobias D.
AU - Kenis, Paul J.A.
AU - Reichert, David E.
N1 - Funding Information:
We are grateful for the funding support from the Department of Energy Office of Biological and Environmental Research , Grant No. DE-FG02-08ER64682 & DE-SC00002032 (fellowship to D. Ranganathan) as well as the National Cancer Institute ( CA161348 ). We also thank the cyclotron facility and staff of the Mallinckrodt Institute of Radiology, Washington University School of Medicine for their support in the production of radioisotopes.
PY - 2013/1
Y1 - 2013/1
N2 - Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Cu
KW - Ga
KW - Microfluidic
KW - PET
KW - RGD
UR - http://www.scopus.com/inward/record.url?scp=84871919085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871919085&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2012.08.012
DO - 10.1016/j.nucmedbio.2012.08.012
M3 - Article
C2 - 23078875
AN - SCOPUS:84871919085
SN - 0969-8051
VL - 40
SP - 42
EP - 51
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -