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Rapid solid phase synthesis and biodistribution of 18F-labelled linear peptides
Julie L Sutcliffe-Goulden1, Michael J O'Doherty, Paul K Marsden
1The Clinical PET Centre, Guy's, King's and St.Thomas' School of Medicine, The Lower Ground Floor, Lambeth Wing, St. Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK. julie.l.sutcliffe@kcl.ac.uk
Summary
A new rapid radiolabelling method enables short peptides, like those targeting integrins, for positron emission tomography (PET) imaging. This 20-minute process yields high purity peptides for potential diagnostic applications.
Area of Science:
- Radiochemistry
- Peptide Synthesis
- Positron Emission Tomography (PET) Imaging
Background:
- Short peptides are valuable for targeted PET imaging, but rapid and efficient radiolabelling remains a challenge.
- Developing novel prosthetic groups and labelling strategies is crucial for advancing peptide-based diagnostics.
Purpose of the Study:
- To develop a rapid and efficient method for radiolabelling short peptides with Fluorine-18 (18F) for PET imaging.
- To evaluate the utility of this method for labelling peptides containing the arginine-glycine-aspartic acid (RGD) motif.
Main Methods:
- Solid-phase peptide synthesis using 9-fluorenylmethoxycarbonyl (Fmoc) chemistry and a hyper acid labile linker.
- In situ labelling of peptides with 4-[18F]fluorobenzoic acid using optimized coupling (HATU/DIPEA) and cleavage (trifluoroacetic acid/phenol/water/Triisopropylsilane) conditions.
- Evaluation of radiochemical yield, purity, and synthesis time; in vitro cell binding inhibition assays; and in vivo biodistribution studies in tumor-bearing mice.
Main Results:
- A rapid radiolabelling method was established, achieving 80%-90% radiochemical yield and >95% purity in 20 minutes without HPLC purification.
- Fluorobenzoyl labelled RGD-containing peptides retained their ability to inhibit integrin-mediated cell binding in vitro.
- In vivo studies showed transient tumor accumulation of labelled peptides, with rapid clearance by liver and kidneys.
Conclusions:
- The developed rapid radiolabelling technique is highly efficient for preparing 18F-labelled peptides for PET imaging.
- This method, particularly when combined with more selective peptides and optimized pharmacokinetics, holds significant promise for enhancing peptide-based PET applications.
- Further development of peptide-based PET agents using this rapid labelling strategy could improve diagnostic capabilities for various diseases.