Investigation of Fluorine-18 Labelled Peptides for Binding to Cholecystokinin-2 Receptors with High Affinity
- Author(s)
- Khan, NUH; Corlett, A; Hutton, CA; Haskali, MB;
- Details
- Publication Year 2022,Volume 28,Issue #1,Page 6
- Journal Title
- International Journal of Peptide Research and Therapeutics
- Publication Type
- Research article
- Abstract
- Many cancers of neuroendocrine origin overexpress cholecystokinin-2 receptors (CCK-2R) including medullary thyroid cancer, small cell lung cancer and other lung carcinoids. Fluorine-18 labelled peptides targeting CCK-2R enable direct visualization and quantification of this receptor in vivo using positron emission tomography imaging. CP04 1 and MG11 2 are two previously described truncated peptides derived from the native CCK-2R hormone ligand, gastrin. The N-terminus of the MG11 2 octopeptide was chemically modified with various fluorine containing aromatic (4-fluorobenzoate), heterocyclic (6-fluoronicotinate) and aliphatic (2-fluoropropionate) moieties. To assess the impact these modifications had on CCK-2R binding, ligand-binding assays were conducted using A431 cells overexpressing human CCK-2R. MG11 2 modified by 4-fluorobenzoate (FB-MG11 3) demonstrated the highest binding affinity (0.20 nM) followed by MG11 2 modified by 6-fluoronicotinate (FNic-MG11 4; 0.74 nM) and 2-fluoropropionate (FP-MG11 5; 1.80 nM), respectively. Whilst indirect labelling of MG11 2 using fluorine-18 labelled activated esters of fluorobenzoate and 6-fluoronicotinate was unsuccessful, direct fluorine-18 labelling at the N-terminus modified with 6-nitronicotinate afforded a 47.6% radiochemical yield of [18F]FNic-MG11. Unfortunately, [18F]FNic-MG11 4 was chemically unstable, decomposing slowly through defluorination, thereby impeding any further work with this radiotracer.
- Department(s)
- Cancer Imaging
- Publisher's Version
- https://doi.org/10.1007/s10989-021-10310-z
- Open Access at Publisher's Site
- https://doi.org/10.1007/s10989-021-10310-z
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-20 02:39:28
Last Modified: 2024-12-20 02:40:52