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

Merchant, S; Allott, L; Carroll, L; Tittrea, V; Kealey, S; Witney, TH; Miller, PW; ... Aboagye, EO; + view all (2016) Synthesis and pre-clinical evaluation of a [18F] fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression. RSC Advances , 62 (6) pp. 57569-57579. 10.1039/c6ra07404a. Green open access

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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.

Type: Article
Title: Synthesis and pre-clinical evaluation of a [18F] fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/c6ra07404a
Publisher version: http://dx.doi.org/10.1039/c6ra07404a
Language: English
Additional information: Copyright © 2016 The Royal Society of Chemistry.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Metabolism and Experi Therapeutics
URI: https://discovery.ucl.ac.uk/id/eprint/1503233
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