title: Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups.
abstract: Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the (18)F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [(18)F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [(18)F]5, and [(18)F]-4-(3-fluoropropoxy)benzaldehyde, [(18)F]9, in addition to the widely used 4-[(18)F]fluorobenzaldehyde, [(18)F]12. The three (18)F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [(18)F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [(18)F]10 or [(18)F]13. The radioactivity from the [(18)F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [(18)F]10 and [(18)F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [(18)F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate.
authors.affiliation: Hammersmith Imanet, Du Cane Road, London W12ONN, UK.
authors.forename: Matthias
authors.initials: M
authors.lastname: Glaser
authors.forename: Matthew
authors.initials: M
authors.lastname: Morrison
authors.forename: Magne
authors.initials: M
authors.lastname: Solbakken
authors.forename: Joseph
authors.initials: J
authors.lastname: Arukwe
authors.forename: Hege
authors.initials: H
authors.lastname: Karlsen
authors.forename: Unni
authors.initials: U
authors.lastname: Wiggen
authors.forename: Sue
authors.initials: S
authors.lastname: Champion
authors.forename: Grete Mørk
authors.initials: GM
authors.lastname: Kindberg
authors.forename: Alan
authors.initials: A
authors.lastname: Cuthbertson
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D001667:Binding, Competitive; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D057927:Hydrophobic and Hydrophilic Interactions; D016023:Integrins / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D049268:Positron-Emission Tomography
chemical_list: D000447:Aldehydes; D005462:Fluorine Radioisotopes; D016023:Integrins; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D011092:Polyethylene Glycols