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.
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Merchant et al Synthesis and pre-clinical evaluation of a 18F fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression.pdf Download (882kB) | Preview |
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 > 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 > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1503233 |
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