Prototypic (18)F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma

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

Journal

Book Volume: 8

Pages Range: 304-309

Journal Issue: 3

DOI: 10.1021/acsmedchemlett.6b00467

Abstract

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.

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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://dx.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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