Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups

Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the F-18-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 [F-18]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)-acetaldehyde, [F-18]5, and [F-18]-4-(3-fluoropropoxy)benzaldehyde, [F-18]9, in addition to the widely used 4-[F-18]fluorobenzaldehyde, [F-18]12. The three F-18-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 [F-18]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 [F-18]10 or [F-18]13. The radioactivity from the [F-18]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 [F-18]10 and [F-18]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 [F-18]5 clearly influences the overall excretion pattern for the RGD peptide conjugate.