Show simple item record

dc.contributor.authorAllott, L
dc.contributor.authorMiranda, C
dc.contributor.authorHayes, A
dc.contributor.authorRaynaud, F
dc.contributor.authorCawthorne, C
dc.contributor.authorSmith, G
dc.date.accessioned2019-02-15T15:31:34Z
dc.date.issued2019-12-01
dc.identifier.citationEJNMMI radiopharmacy and chemistry, 2019, 4 (1), pp. 1 - ?
dc.identifier.issn2365-421X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3051
dc.identifier.eissn2365-421X
dc.identifier.doi10.1186/s41181-018-0054-z
dc.description.abstractBACKGROUND: The histological evaluation of estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer lesions from biopsy tissue can stratify patients to receive endocrine therapy. Furthermore, PR expression can predict response to selective estrogen receptor modulators (SERMs). Current immunohistochemical approaches to PR detection are limited by sampling error associated with biopsy and lack of standardised protocols; positron emission tomography (PET) using receptor targeted radiopharmaceuticals to provide quantitative, whole-body imaging may overcome these limitations. PR expression has been successfully imaged with PET in the clinical setting, however investigation into new radioligands with improved pharmacokinetics and metabolic stability is desirable. RESULTS: We report the synthesis of a focused library of non-steroidal PR ligands evaluated for use as PET radioligands. A lead candidate ([18F]2) with low nanomolar activity was selected and radiolabelled with a radiochemical yield of 2.29 ± 2.31% (decay-corrected), radiochemical purity (RCP) > 95% and a molar activity of 2.5 ± 1.6 GBq/μmol. Cell uptake studies showed a significant and specific accumulation of [18F]2 in T47D (PR++) breast cancer cell compared to MDA-MB-231 (PR-) control; however, in vivo evaluation was confounded by rapid defluorination of the radioligand. In vitro metabolite analysis of 2 in MLM confirmed defluorination and oxidative metabolism of the thiocarbamate to oxocarbamate moiety by mass spectrometry. CONCLUSIONS: A route to access [18F]2 was developed to allow in vitro and in vivo evaluation, albeit with low radiochemical yield and modest molar activity. [18F]2 demonstrated selective uptake in PR++ T47D cells which could be blocked in a dose dependent manner with progesterone. However, [18F]2 showed poor in vivo metabolic stability with rapid defluorination within the time frame of the imaging protocol.
dc.formatElectronic
dc.format.extent1 - ?
dc.languageeng
dc.language.isoeng
dc.publisherSPRINGERNATURE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSynthesis of a benzoxazinthione derivative of tanaproget and pharmacological evaluation for PET imaging of PR expression.
dc.typeJournal Article
dcterms.dateAccepted2018-12-10
rioxxterms.versionofrecord10.1186/s41181-018-0054-z
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEJNMMI radiopharmacy and chemistry
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/PET Radiochemistry
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/PET Radiochemistry
pubs.publication-statusPublished
pubs.volume4
pubs.embargo.termsNot known
icr.researchteamPET Radiochemistry
dc.contributor.icrauthorRaynaud, Florence
dc.contributor.icrauthorSmith, Graham


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0