Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers

Abstract OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate di...

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Autores principales:	Sarah E. Lochrin, Baris Turkbey, Billel Gasmi, Keith Schmidt, Jonathan D. Strope, Cindy H. Chau, Tristan M. Sissung, Douglas K. Price, Lisa Cordes, Suzana Markolovic, Bradford J. Wood, Peter A. Pinto, Yolanda L. McKinney, Joanna H. Shih, Elliot Levy, Ravi Madan, William Dahut, Peter L. Choyke, Maria Merino, William D. Figg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2155571997884125817fef4e6bd235ee
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spelling	oai:doaj.org-article:2155571997884125817fef4e6bd235ee2021-12-02T13:20:14ZPilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers10.1038/s41598-021-84960-w2045-2322https://doaj.org/article/2155571997884125817fef4e6bd235ee2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84960-whttps://doaj.org/toc/2045-2322Abstract OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p < 0.0078). The localized cancer subgroup (n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer.Sarah E. LochrinBaris TurkbeyBillel GasmiKeith SchmidtJonathan D. StropeCindy H. ChauTristan M. SissungDouglas K. PriceLisa CordesSuzana MarkolovicBradford J. WoodPeter A. PintoYolanda L. McKinneyJoanna H. ShihElliot LevyRavi MadanWilliam DahutPeter L. ChoykeMaria MerinoWilliam D. FiggNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah E. Lochrin Baris Turkbey Billel Gasmi Keith Schmidt Jonathan D. Strope Cindy H. Chau Tristan M. Sissung Douglas K. Price Lisa Cordes Suzana Markolovic Bradford J. Wood Peter A. Pinto Yolanda L. McKinney Joanna H. Shih Elliot Levy Ravi Madan William Dahut Peter L. Choyke Maria Merino William D. Figg Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
description	Abstract OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p < 0.0078). The localized cancer subgroup (n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer.
format	article
author	Sarah E. Lochrin Baris Turkbey Billel Gasmi Keith Schmidt Jonathan D. Strope Cindy H. Chau Tristan M. Sissung Douglas K. Price Lisa Cordes Suzana Markolovic Bradford J. Wood Peter A. Pinto Yolanda L. McKinney Joanna H. Shih Elliot Levy Ravi Madan William Dahut Peter L. Choyke Maria Merino William D. Figg
author_facet	Sarah E. Lochrin Baris Turkbey Billel Gasmi Keith Schmidt Jonathan D. Strope Cindy H. Chau Tristan M. Sissung Douglas K. Price Lisa Cordes Suzana Markolovic Bradford J. Wood Peter A. Pinto Yolanda L. McKinney Joanna H. Shih Elliot Levy Ravi Madan William Dahut Peter L. Choyke Maria Merino William D. Figg
author_sort	Sarah E. Lochrin
title	Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
title_short	Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
title_full	Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
title_fullStr	Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
title_full_unstemmed	Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
title_sort	pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2155571997884125817fef4e6bd235ee
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Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers

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