Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers
| Autor: | William D. Figg, Elliot Levy, Billel Gasmi, Baris Turkbey, Tristan M. Sissung, Lisa M. Cordes, Peter L. Choyke, Maria Merino, Cindy H. Chau, Yolanda McKinney, Jonathan D. Strope, Douglas K. Price, Keith T. Schmidt, Peter A. Pinto, Joanna H. Shih, Bradford J. Wood, Sarah E Lochrin, Suzana Markolovic, Ravi A. Madan, William L. Dahut |
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| Rok vydání: | 2021 |
| Předmět: |
Gadolinium DTPA
Male 0301 basic medicine Oncology medicine.medical_specialty Contrast enhancement Genotype Science Pilot Projects Single Center Article Tumour biomarkers Gadoxetate Disodium Solute Carrier Organic Anion Transporter Family Member 1B3 03 medical and health sciences Prostate cancer 0302 clinical medicine Text mining Prostate Internal medicine medicine Humans Neoplasm Metastasis Multidisciplinary business.industry Prostatic Neoplasms medicine.disease Magnetic Resonance Imaging 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Medicine Immunohistochemistry Biomarker (medicine) Cancer imaging business |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-021-84960-w |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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