TY - JOUR
T1 - Optimization of the solid-phase synthesis of [18F] radiolabeled peptides for positron emission tomography
AU - White, Jason B.
AU - Hausner, Sven H.
AU - Carpenter, Richard D.
AU - Sutcliffe, Julie
PY - 2012/12
Y1 - 2012/12
N2 - Establishing improved methods for the radiolabeling of peptides with fluorine-18 via solid-phase peptide synthesis (SPPS) is desirable for the efficient synthesis of peptide-based molecular imaging agents. This work focuses on the development of a standardized platform to facilitate the reliable and efficient synthesis of high-purity fluorine-18 radiolabeled peptides for in vivo imaging with positron emission tomography (PET). Seven commercially available resins were selected for solid-phase radiolabeling of the model peptide VQAAIDYING with 4-[18F]fluorobenzoic acid ([18F]FBA). A wide range of radiochemical yields (18.8±1.5% to 41.2±5.3%) was obtained using standard conditions (coupling: 3eq amino acid, 3eq HATU, 6eq DIPEA, 1.5h, r.t.; cleavage: 94% TFA, 3h, r.t.). After modification of coupling reagents and employing heated reactions to 37°C, radiochemical yields were improved by as much as 35.3% over standard conditions. When the optimized conditions were applied to the synthesis of [18F]FBA-PEG28-A20FMDV2, which targets the αvΒ6 integrin in vivo, radiochemical yields improved by as much as 73.4% over those obtained using standard coupling and cleavage conditions. This platform can be utilized to improve the synthesis of peptide-based molecular probes for molecular imaging with PET.
AB - Establishing improved methods for the radiolabeling of peptides with fluorine-18 via solid-phase peptide synthesis (SPPS) is desirable for the efficient synthesis of peptide-based molecular imaging agents. This work focuses on the development of a standardized platform to facilitate the reliable and efficient synthesis of high-purity fluorine-18 radiolabeled peptides for in vivo imaging with positron emission tomography (PET). Seven commercially available resins were selected for solid-phase radiolabeling of the model peptide VQAAIDYING with 4-[18F]fluorobenzoic acid ([18F]FBA). A wide range of radiochemical yields (18.8±1.5% to 41.2±5.3%) was obtained using standard conditions (coupling: 3eq amino acid, 3eq HATU, 6eq DIPEA, 1.5h, r.t.; cleavage: 94% TFA, 3h, r.t.). After modification of coupling reagents and employing heated reactions to 37°C, radiochemical yields were improved by as much as 35.3% over standard conditions. When the optimized conditions were applied to the synthesis of [18F]FBA-PEG28-A20FMDV2, which targets the αvΒ6 integrin in vivo, radiochemical yields improved by as much as 73.4% over those obtained using standard coupling and cleavage conditions. This platform can be utilized to improve the synthesis of peptide-based molecular probes for molecular imaging with PET.
KW - Fluorine-18
KW - Peptides
KW - Positron emission tomography
KW - Radiolabeling
KW - Solid-phase
UR - http://www.scopus.com/inward/record.url?scp=84866786863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866786863&partnerID=8YFLogxK
U2 - 10.1016/j.apradiso.2012.08.003
DO - 10.1016/j.apradiso.2012.08.003
M3 - Article
C2 - 23041391
AN - SCOPUS:84866786863
VL - 70
SP - 2720
EP - 2729
JO - Applied Radiation and Isotopes
JF - Applied Radiation and Isotopes
SN - 0969-8043
IS - 12
ER -