Keller M, Maschauer S, Brennauer A, Tripal P, Koglin N, Dittrich R, Bernhardt G, Kuwert T, Wester HJ, Buschauer A, Prante O (2017)
Publication Type: Journal article
Publication year: 2017
Book Volume: 8
Pages Range: 304-309
Journal Issue: 3
DOI: 10.1021/acsmedchemlett.6b00467
The neuropeptide Y (NPY) Y1 receptor (Y1R) selective radioligand (R)-N(?)-(2,2-diphenylacetyl)-N(?)-[4-(2-[(18)F]fluoropropanoylamino)butyl]aminocarbonyl-N-(4-hydroxybenzyl)argininamide ([(18)F]23), derived from the high-affinity Y1R antagonist BIBP3226, was developed for imaging studies of Y1R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y1R affinity. The fluoropropanoylated derivative 23 displayed high affinity (Ki = 1.3 nM) and selectivity toward Y1R. Radiosynthesis was accomplished via (18)F-fluoropropanoylation, yielding [(18)F]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, [(18)F]23 was successfully used for imaging of Y1R positive MCF-7 tumors in nude mice. Therefore, we suggest [(18)F]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y1R-dependent enrichment in mammary carcinoma.
APA:
Keller, M., Maschauer, S., Brennauer, A., Tripal, P., Koglin, N., Dittrich, R.,... Prante, O. (2017). Prototypic (18)F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma. ACS Medicinal Chemistry Letters, 8(3), 304-309. https://doi.org/10.1021/acsmedchemlett.6b00467
MLA:
Keller, Max, et al. "Prototypic (18)F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma." ACS Medicinal Chemistry Letters 8.3 (2017): 304-309.
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