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

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

  • Mol Imaging Biol. 2019 Apr;21(2):257-268. doi: 10.1007/s11307-018-1212-0.
Cécile Philippe 1 2,  Markus Zeilinger 1 3,  Monika Dumanic 1,  Florian Pichler 1 3,  Lukas Fetty 1 4,  Chrysoula Vraka 1,  Theresa Balber 1,  Wolfgang Wadsak 1 5 6,  Katharina Pallitsch 7,  Helmut Spreitzer 8,  Rupert Lanzenberger 9,  Marcus Hacker 1,  Markus Mitterhauser 10 11 12
Affiliations

Affiliations

  • 1 Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • 2 Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
  • 3 Faculty of Engineering, University of Applied Sciences Wiener Neustadt, Neustadt, Austria.
  • 4 Department of Radiotherapy, Division of Medical Physics, Medical University of Vienna, Vienna, Austria.
  • 5 Department of Inorganic Chemistry, University of Vienna, Vienna, Austria.
  • 6 CBmed, Graz, Austria.
  • 7 Department of Organic Chemistry, University of Vienna, Vienna, Austria.
  • 8 Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
  • 9 Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
  • 10 Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. [email protected].
  • 11 Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria. [email protected].
  • 12 Ludwig Boltzmann Institute Applied Diagnostics, Vienna, Austria. [email protected].
PMID: 29948643 DOI: 10.1007/s11307-018-1212-0
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.

Keywords

Ex vivo; In vitro; In vivo; MCHR1; PET; Small animal imaging; [11C]SNAP-7941; [18F]FE@SNAP.

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