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

Glaser, M., Morrison, M., Solbakken, M., Arukwe, J., Karlsen, H., Wiggen, U., Champion, S. , Kindberg, G.M. and Cuthbertson, A. (2008) Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [¹⁸F] fluorinated aldehyde-containing prosthetic groups. Bioconjugate Chemistry, 19(4), pp. 951-957. (doi: 10.1021/bc700472w)

Abstract

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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Champion, Dr Sue
• Authors: Glaser, M., Morrison, M., Solbakken, M., Arukwe, J., Karlsen, H., Wiggen, U., Champion, S., Kindberg, G.M., and Cuthbertson, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Bioconjugate Chemistry
• ISSN: 1043-1802
• Published Online: 15 March 2008