Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/29408
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dc.contributor.authorChan, CY-
dc.contributor.authorHopkins, SL-
dc.contributor.authorGuibbal, F-
dc.contributor.authorPacelli, A-
dc.contributor.authorBaguña Torres, J-
dc.contributor.authorMosley, M-
dc.contributor.authorLau, D-
dc.contributor.authorIsenegger, P-
dc.contributor.authorChen, Z-
dc.contributor.authorWilson, TC-
dc.contributor.authorDias, G-
dc.contributor.authorHueting, R-
dc.contributor.authorGouverneur, V-
dc.contributor.authorCornelissen, B-
dc.date.accessioned2024-07-25T13:59:53Z-
dc.date.available2024-07-25T13:59:53Z-
dc.date.issued2022-10-09-
dc.identifierORCiD: Doreen Lau https://orcid.org/0000-0002-7623-2401-
dc.identifierORCiD: Bart Cornelissen http://orcid.org/0000-0001-7581-3303-
dc.identifier67-
dc.identifier.citationChan, C.Y. et al. (2022) 'Correlation between molar activity, injection mass and uptake of the PARP targeting radiotracer [<sup>18</sup>F]olaparib in mouse models of glioma', EJNMMI Research, 12 (1), 67, pp. 1 - 10. doi: 10.1186/s13550-022-00940-9.en_US
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/29408-
dc.descriptionSupplementary information is available online at: https://ejnmmires.springeropen.com/articles/10.1186/s13550-022-00940-9#Sec15 .en_US
dc.description.abstractPurpose: Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [<sup>18</sup>F]olaparib and the injected mass of [<sup>Total</sup>F]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models. Methods: [<sup>18</sup>F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [<sup>Total</sup>F]olaparib (varying injected mass: 0.04–8.0 µg, and molar activity: 1–320 GBq/μmol). Results: Selective uptake of [<sup>18</sup>F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [<sup>Total</sup>F]olaparib (µg) but not the molar activity. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [<sup>Total</sup>F]olaparib resulted in lower relative tumour uptake (%ID/g; P < 0.05). Ex vivo analysis of U87MG xenograft sections showed that the heterogeneity in [<sup>18</sup>F]olaparib intratumoural uptake correlated with PARP1 expression. Substantial upregulation of PARP1-3 expression was observed after administration of [<sup>Total</sup>F]olaparib (> 0.5 µg). Conclusion: Our findings show that the injected mass of [<sup>Total</sup>F]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy.en_US
dc.description.sponsorshipPancreatic Cancer U.K.; the Pancreatic Cancer Research Fund; CRUK through the Oxford Institute for Radiation Oncology, the CRUK Oxford Centre, and the CRUK/EPSRC Imaging Centre in Oxford; the EPSRC (EP/L025604/1, NS/A000024/1); and CRUK C5255/A16466.en_US
dc.format.extent1 - 10-
dc.format.mediumElectronic-
dc.languageEnglish-
dc.language.isoenen_US
dc.publisherSpringerOpen (part of Springer Nature)en_US
dc.rightsCopyright © The Author(s) 2022. Rights and permissions: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.titleCorrelation between molar activity, injection mass and uptake of the PARP targeting radiotracer [<sup>18</sup>F]olaparib in mouse models of gliomaen_US
dc.title.alternativeCorrelation between molar activity, injection mass and uptake of the PARP targeting radiotracer [18F]olaparib in mouse models of gliomaen_US
dc.typeArticleen_US
dc.date.dateAccepted2022-09-30-
dc.identifier.doihttps://doi.org/10.1186/s13550-022-00940-9-
dc.relation.isPartOfEJNMMI Research-
pubs.issue1-
pubs.publication-statusPublished-
pubs.volume12-
dc.identifier.eissn2191-219X-
dc.rights.licensehttps://creativecommons.org/licenses/by/4.0/legalcode.en-
dc.rights.holderThe Author(s)-
Appears in Collections:Dept of Life Sciences Research Papers

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