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Open Access 01-04-2019 | Research Article

SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [¹⁸F]FE@SNAP and [¹¹C]SNAP-7941

Authors: Cécile Philippe, Markus Zeilinger, Monika Dumanic, Florian Pichler, Lukas Fetty, Chrysoula Vraka, Theresa Balber, Wolfgang Wadsak, Katharina Pallitsch, Helmut Spreitzer, Rupert Lanzenberger, Marcus Hacker, Markus Mitterhauser

Published in: Molecular Imaging and Biology | Issue 2/2019

Abstract

Purpose

The melanin-concentrating hormone receptor 1 (MCHR1) has become an important pharmacological target, since it may be involved in various diseases, such as diabetes, insulin resistance, and obesity. Hence, a suitable positron emission tomography radiotracer for the in vivo assessment of the MCHR1 pharmacology is imperative. The current paper contrasts the extensive in vitro, in vivo, and ex vivo assessments of the radiotracers [¹⁸F]FE@SNAP and [¹¹C]SNAP-7941 and provides comprehensive information about their biological and physicochemical properties. Furthermore, it examines their suitability for first-in-man imaging studies.

Procedures

Kinetic real-time cell-binding studies with [¹⁸F]FE@SNAP and [¹¹C]SNAP-7941 were conducted on adherent Chines hamster ovary (CHO-K1) cells stably expressing the human MCHR1 and MCHR2. Small animal imaging studies on mice and rats were performed under displacement and baseline conditions, as well as after pretreatment with the P-glycoprotein/breast cancer resistant protein inhibitor tariquidar. After the imaging studies, detailed analyses of the ex vivo biodistribution were performed. Ex vivo metabolism was determined in rat blood and brain and analyzed at various time points using a quantitative radio-HPLC assay.

Results

[¹¹C]SNAP-7941 demonstrates high uptake on CHO-K1-hMCHR1 cells, whereas no uptake was detected for the CHO-K1-hMCHR2 cells. In contrast, [¹⁸F]FE@SNAP evinced binding to CHO-K1-hMCHR1 and CHO-K1-hMCHR2 cells. Imaging studies with [¹⁸F]FE@SNAP and [¹¹C]SNAP-7941 showed an increased brain uptake after tariquidar pretreatment in mice, as well as in rats, and exhibited a significant difference between the time-activity curves of the baseline and blocking groups. Biodistribution of both tracers demonstrated a decreased uptake after displacement. [¹¹C]SNAP-7941 revealed a high metabolic stability in rats, whereas [¹⁸F]FE@SNAP was rapidly metabolized.

Conclusions

Both radiotracers demonstrate appropriate imaging properties for the MCHR1. However, the pronounced metabolic stability as well as superior selectivity and affinity of [¹¹C]SNAP-7941 underlines the decisive superiority over [¹⁸F]FE@SNAP.

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Title: SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [18F]FE@SNAP and [11C]SNAP-7941
Authors: Cécile Philippe
Markus Zeilinger
Monika Dumanic
Florian Pichler
Lukas Fetty
Chrysoula Vraka
Theresa Balber
Wolfgang Wadsak
Katharina Pallitsch
Helmut Spreitzer
Rupert Lanzenberger
Marcus Hacker
Markus Mitterhauser
Publication date: 01-04-2019
Publisher: Springer International Publishing
Published in: Molecular Imaging and Biology / Issue 2/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1212-0

ACC 2024 Congress

Springer Medicine

SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [¹⁸F]FE@SNAP and [¹¹C]SNAP-7941

Abstract

Purpose

Procedures

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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