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

Anna Pees; Wissam Beaino; Esther J M Kooijman; Maxime Schreurs; Mariska Verlaan; Robert C Schuit; Maria J W D Vosjan; Anton F Engelsman; Albert D Windhorst; Danielle J Vugts

doi:10.1016/j.nucmedbio.2021.10.003

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

Nucl Med Biol. 2021 Nov-Dec:102-103:97-105. doi: 10.1016/j.nucmedbio.2021.10.003. Epub 2021 Oct 29.

Affiliations

¹ Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands.
² BV Cyclotron VU, De Boelelaan 1081, 1081 HV Amsterdam, the Netherlands.
³ Amsterdam UMC, VU Medical Center, Department of Surgery, Amsterdam, the Netherlands.
⁴ Amsterdam UMC, VU University, Radiology and Nuclear Medicine, Radionuclide Center, De Boelelaan 1085c, Amsterdam, the Netherlands. Electronic address: d.vugts@amsterdamumc.nl.

PMID: 34743064
DOI: 10.1016/j.nucmedbio.2021.10.003

Abstract

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: [¹⁸F]Cinacalcet was synthesized by copper-catalysed [¹⁸F]trifluoromethylation of a boronic acid precursor using high molar activity [¹⁸F]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: [¹⁸F]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 [¹⁸F]cinacalcet to the CaSR could not be confirmed.

Conclusions: [¹⁸F]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.

Keywords: Calcimimetic; Calcium-sensing receptor; Cinacalcet; Parathyroid hyperplasia; Pre-operative localization; [(18)F]trifluoromethylation.

MeSH terms

Cinacalcet*

Substances

Cinacalcet