Keller, Max and Maschauer, Simone and Brennauer, Albert and Tripal, Philipp and Koglin, Norman and Dittrich, Ralf and Bernhardt, Guenther and Kuwert, Torsten and Wester, Hans-Juergen and Buschauer, Armin and Prante, Olaf (2017) Prototypic F-18-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma. ACS MEDICINAL CHEMISTRY LETTERS, 8 (3). pp. 304-309. ISSN 1948-5875,
Full text not available from this repository. (Request a copy)Abstract
The neuropeptide Y (NPY) Y-1, receptor (Y-1,R) selective radioligand (R)-N-a -(2,2-diphenylacety1)N-omega-[4(2[F-18]fluoropropanoylamino)butyllaminocarbonyl-N-(4-hydroxybenzy1)-argininamide ([F-18]23), derived from the high-affinity Y-1,R antagonist BIBP3226, was developed for imaging studies of Y-1,R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y-1,R affinity. The fluoropropanoylated derivative 23 displayed high affinity (K-i = 1.3 nM) and selectivity toward Y1R Radiosynthesis was accomplished via F-18-fluoropropanoylation, yielding [F-18]23 with excellent stability in mice; however, the biodistribution study revealed pronounced hepatobiliary clearance with high accumulation in the gall bladder (>100 %ID/g). Despite the unfavorable biodistribution, [F-18]123 was successfully used for imaging of Y,R positive MCF-7 tumors in nude mice. Therefore, we suggest [F-18]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y-1,R-dependent enrichment in mammary carcinoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Y-1 RECEPTOR ANTAGONISTS; ACYLGUANIDINE BIOISOSTERIC APPROACH; POSITRON-EMISSION-TOMOGRAPHY; TARGETED TUMOR-DIAGNOSIS; BREAST-CANCER; PEPTIDE-HORMONES; HIGHLY POTENT; THERAPY; NEUROTENSIN; ANALOGS; Fluorine-18; antagonist; positron emission tomography; PET; neuropeptide Y; NPY; Y1R |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:00 |
| Last Modified: | 20 Feb 2019 10:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/263 |
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