Ultra-early changes in vascular parameters from dynamic contrast enhanced MRI of breast cancer xenografts following systemic therapy with doxorubicin and liver X receptor agonist Article Swipe
Kathinka E. Pitman
,
Kine Mari Bakke
,
Alexandr Kristian
,
Eirik Malinen
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1186/s40644-019-0280-y
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1186/s40644-019-0280-y
Background Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) may be used to depict tumour vascular structure and for therapy response assessment in various tumour sites. The purpose of the current work is to examine whether ultra-early changes in tumour physiology following cytotoxic treatment with doxorubicin and liver X receptor (LXR) agonist GW3965 are detectable by DCE-MRI. Methods 36 female, athymic nude foxn1nu mice with bilaterally implanted breast cancer xenografts (17 with ER-positive HBCx34, 19 with triple-negative HBCx39) were randomised in the following treatment groups; control, GW3965 (40 mg/kg p.o.), doxorubicin (8 mg/kg i.v.) and a combination therapy of GW3965 and doxorubicin. DCE-MRI (3D FLASH on a 7 T preclinical scanner) was performed at baseline and one and six days after onset of treatment. Wash-in (30 s p.i.) and wash-out (300 s p.i.) enhancement were quantified from dynamic uptake curves, before voxel-by-voxel fitting to the pharmacokinetic Tofts model and generation of maps for the resulting parameters K trans , ν e and ν B . Treatment effect was evaluated by univariate repeated measures mixed-effects maximum likelihood regression models applied to median tumour data. Results We found no effects of any treatment 24 h post treatment. After 6 days, doxorubicin given as both mono- and combination therapy gave significant increases of ~ 30% in wash-in enhancement ( p < 0.011) and K trans ( p < 0.017), and 40–50% in ν B ( p < 0.024) for HBCx34, but not for HBCx39. No effects of GW3965 were observed at any time ( p > 0.1). Conclusions Twenty-four h after onset of treatment was too early to evaluate treatment effects by DCE-MRI. Early enhancement and K trans were approximately equally sensitive metrics to capture treatment effects six days pt. Pharmacokinetic modelling however allowed us to attribute the observed effect to changes in tumour perfusion rather than increased retention.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s40644-019-0280-y
- https://cancerimagingjournal.biomedcentral.com/track/pdf/10.1186/s40644-019-0280-y
- OA Status
- gold
- Cited By
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- References
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- Related Works
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- OpenAlex ID
- https://openalex.org/W2995988973
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- OpenAlex ID
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https://openalex.org/W2995988973Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1186/s40644-019-0280-yDigital Object Identifier
- Title
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Ultra-early changes in vascular parameters from dynamic contrast enhanced MRI of breast cancer xenografts following systemic therapy with doxorubicin and liver X receptor agonistWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-12-01Full publication date if available
- Authors
-
Kathinka E. Pitman, Kine Mari Bakke, Alexandr Kristian, Eirik MalinenList of authors in order
- Landing page
-
https://doi.org/10.1186/s40644-019-0280-yPublisher landing page
- PDF URL
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https://cancerimagingjournal.biomedcentral.com/track/pdf/10.1186/s40644-019-0280-yDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://cancerimagingjournal.biomedcentral.com/track/pdf/10.1186/s40644-019-0280-yDirect OA link when available
- Concepts
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Medicine, Doxorubicin, Breast cancer, Agonist, Dynamic contrast, Magnetic resonance imaging, Systemic therapy, Pathology, Cancer, Cancer research, Internal medicine, Oncology, Chemotherapy, Receptor, RadiologyTop concepts (fields/topics) attached by OpenAlex
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6Total citation count in OpenAlex
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2022: 5, 2020: 1Per-year citation counts (last 5 years)
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27Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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