Synthesis and evaluation of [ 18 F]cinacalcet for the imaging of parathyroid hyperplasia.

Autor: Pees A; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Beaino W; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Kooijman EJM; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Schreurs M; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Verlaan M; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Schuit RC; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Vosjan MJWD; BV Cyclotron VU, De Boelelaan 1081, 1081 HV Amsterdam, the Netherlands., Engelsman AF; Amsterdam UMC, VU Medical Center, Department of Surgery, Amsterdam, the Netherlands., Windhorst AD; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands., Vugts DJ; Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands. Electronic address: d.vugts@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2021 Nov-Dec; Vol. 102-103, pp. 97-105. Date of Electronic Publication: 2021 Oct 29.
DOI: 10.1016/j.nucmedbio.2021.10.003
Abstrakt: Introduction: Parathyroid hyperplasia is a disease characterized by overactive parathyroid glands secreting increased levels of parathyroid hormone. Surgical removal of the parathyroid glands is the standard treatment but requires precise pre-operative localization of the glands. However, currently available imaging modalities show limited sensitivity. Since positron emission tomography (PET) is a molecular imaging technique with high accuracy and sensitivity, our aim was to develop a new PET tracer for overactive parathyroid glands imaging by radiolabelling cinacalcet, a drug binding to the calcium-sensing receptor of the parathyroid glands.
Methods: [ 18 F]Cinacalcet was synthesized by copper-catalysed [ 18 F]trifluoromethylation of a boronic acid precursor using high molar activity [ 18 F]fluoroform. Ex vivo biodistribution and metabolism were evaluated in 12 healthy male Wistar rats at 5, 15, 45 and 90 min. PET scans were performed at baseline and after blocking with NPS R-568.
Results: [ 18 F]Cinacalcet was obtained in an overall radiosynthesis time of 1 h with a radiochemical purity of 98 ± 1%, a radiochemical yield of 8 ± 4% (overall, n = 7, corrected for decay) and a molar activity of 40 ± 11 GBq/μmol (n = 7, at EOS). The ex vivo biodistribution showed uptake in the thyroid and parathyroid glands as well as in other glands such as adrenals, salivary glands and pancreas. The tracer was rapidly cleared from the blood via liver and kidneys and showed fast metabolism. PET images confirmed uptake in the target organ. However, in a blocking study with NPS R-568 specific binding of [ 18 F]cinacalcet to the CaSR could not be confirmed.
Conclusions: [ 18 F]Cinacalcet was successfully synthesized. First in vivo experiments in healthy rats showed uptake of the tracer in the target organ and fast metabolism, encouraging further in vivo evaluation of this tracer.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Albert D. Windhorst, co-author of this manuscript, is editor-in-chief of Nuclear Medicine and Biology. He was not involved in the review process of this manuscript to avoid any potential conflict of interest.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: