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SNAPshots of the MCHR1: a Comparison Between the PET-Tracers [18F]FE@SNAP and [11C]SNAP-7941
- Source :
- Molecular Imaging and Biology
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
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.
- Subjects :
- Fluorine Radioisotopes
Cancer Research
Biodistribution
Tariquidar
Hamster
[18F]FE@SNAP
CHO Cells
Pharmacology
Chromatography, Affinity
030218 nuclear medicine & medical imaging
Mice
03 medical and health sciences
Cricetulus
0302 clinical medicine
In vitro
Piperidines
In vivo
Cricetinae
medicine
Animals
Humans
Tissue Distribution
Radiology, Nuclear Medicine and imaging
SNAP-7941
Carbon Radioisotopes
Receptors, Somatostatin
MCHR1
medicine.diagnostic_test
Chemistry
[11C]SNAP-7941
Blood Proteins
Ex vivo
Rats
Kinetics
PET
Pyrimidines
Oncology
Positron emission tomography
Positron-Emission Tomography
Metabolome
Small animal imaging
Research Article
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 18602002 and 15361632
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular Imaging and Biology
- Accession number :
- edsair.doi.dedup.....e1112bc4ca64400debbf0d663b4ab947
- Full Text :
- https://doi.org/10.1007/s11307-018-1212-0