Radiosynthesis and Biodistribution of Cyclic RGD Peptides Conjugated with Novel [18F]Fluorinated Aldehyde-Containing Prosthetic Groups

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• 作者：Matthias Glaser ; Matthew Morrison ; Magne Solbakken ; Joseph Arukwe ; Hege Karlsen ; Unni Wiggen ; Sue Champion ; Grete Mø ; rk Kindberg ; Alan Cuthbertson
• 刊名：Bioconjugate Chemistry
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：19
• 期：4
• 页码：951 - 957
• 全文大小：231K
• 年卷期：v.19,no.4(April 2008)
• ISSN：1520-4812

文摘

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.