Synthesis and pre-clinical evaluation of a [18F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression

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Title: Synthesis and pre-clinical evaluation of a [<sup>18</sup>F]fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression
Author(s): Merchant, S
Allott, L
Carroll, L
Tittrea, V
Kealey, S
Witney, TH
Miller, PW
Smith, G
Aboagye, EO
Item Type: Journal Article
Abstract: The estrogen receptor (ER) and progesterone receptor (PR) are over-expressed in ∼50% of breast cancer lesions, and used as biomarkers to stratify patients for endocrine therapy. Currently, immunohistochemical (IHC) assessment of these lesions from a core-needle biopsy in deep-sited metastases has limitations associated with sampling error and lack of standardization. An alternative solution is positron emission tomography (PET)-based probes, which are inherently quantitative and capable of imaging the entire tumor, including metastases. This work features the synthesis and biological evaluation of a novel fluorinated derivative of tanaproget, a high affinity non-steroidal PR ligand, as a candidate for imaging PR expression in vivo. Radiolabeling of the candidate was achieved in a 15% ± 4 radiochemical yield (non-decay corrected) in one step from [18F]fluoromethyltosylate in 30 min. Cell uptake studies showed a significant difference between the radioligand uptake in PR+ and PR- cell lines; however, in vivo imaging was confounded by defluorination hypothesized to occur via iminium salt formation. Investigation into high affinity, metabolically stable non-steroidal PR ligands is currently ongoing.
Publication Date: 6-Jun-2016
Date of Acceptance: 19-May-2016
URI: http://hdl.handle.net/10044/1/38740
DOI: https://dx.doi.org/10.1039/c6ra07404a
ISSN: 2046-2069
Publisher: Royal Society of Chemistry
Start Page: 57569
End Page: 57579
Journal / Book Title: RSC Advances
Volume: 6
Issue: 62
Sponsor/Funder: Cancer Research UK
Engineering & Physical Science Research Council (E
Funder's Grant Number: C2536/A16584
EP/L025140/1
Copyright Statement: © The Royal Society of Chemistry 2016
Keywords: Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
POSITRON-EMISSION-TOMOGRAPHY
HUMAN-BREAST-CANCER
ESTROGEN-RECEPTOR
AGONIST TANAPROGET
ENDOCRINE THERAPY
PET
CARCINOMA
AFFINITY
ANALOGS
LIGAND
Publication Status: Published
Appears in Collections:Division of Surgery
Chemistry
Catalysis and Advanced Materials
Division of Cancer
Faculty of Medicine
Faculty of Natural Sciences



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