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Cited by 21Mass Spectrometry Techniques and ApplicationsHepatocellular Carcinoma Treatment and PrognosisOptical Imaging and Spectroscopy Techniques

Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging

Open access
Fuchs, Katrin, Kiss, Andras, Bize, Pierre E., Duran, Rafael, Denys, Alban, Hopfgartner, Gérard, Borchard, Gerrit, Jordan, Olivier·2018·Journal of Controlled Release
DOI 10.1016/j.jconrel.2017.10.042
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Abstract

This study describes the use of fluorescence imaging and mass spectrometry imaging, for imaging the anti-angiogenic drug sunitinib, used to treat liver cancer. These techniques allowed for the assessment of local delivery of the unlabeled therapeutic drug. More specifically, the spatial distribution of the drug and its metabolites after local administration was investigated, and drug levels in tumor and liver tissue over time were quantified. For this purpose, sunitinib-eluting microspheres were locoregionally injected into the tumor feeding arteries of rabbits bearing liver tumors. In adjacent areas of tumor and non-targeted contralateral liver tissue, sunitinib distribution was mapped around beads in occluded vessels 7, 12, 13 and 14days after embolization by means of the two imaging methods. Presence of sunitinib metabolites was assessed by mass spectrometry imaging. Sunitinib was found around microspheres in the tumor at day 7, 12, and 13. The drug was retained by the necrotic tumor tissue, resulting in homogeneously distributed and high levels of up to 40μg/g tissue in a 1.5mm radius around the beads. The drug was almost completely eliminated from the contralateral liver tissue. Several of the drug's metabolites, including its primary active metabolite SU12662, were detected in the tumor tissue over 13days. Sunitinib diffused from the beads and was retained at high, therapeutic levels during 13days. This was confirmed independently by complementary fluorescence and mass spectrometry imaging, which served as tools to confirm effective drug delivery after hepatic transarterial administration in situ. Compound: Sunitinib: PubChem CID 5329102.

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  • Fluorescence MSI has been integrated to depict local drug release and record unlabeled therapeutic drug circulation, which is offered to track drug metabolites.

    “Fluorescence MSI has been integrated to depict local drug release and record unlabeled therapeutic drug circulation, which is offered to track the drug metabolites [140].”

    From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [140]

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Authors
Fuchs, K., Kiss, A., Bize, P. E., Duran, R., Denys, A., Hopfgartner, G., Borchard, G., & Jordan, O.
Affiliations
  • University of Geneva (CH)
  • Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author
Jordan, Olivier
ORCID
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2018-01
Volume
269
Pages
128-135
ISSN
0168-3659 (ISSN-L)
DOI
10.1016/j.jconrel.2017.10.042
OpenAlex
W2766494800
Cited by
21
References
24
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc-nd)
Funders
Biocompatibles Ltd.
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
Keywords
sunitinib, liver tumors, hepatic artery embolization, microspheres, drug distribution, drug metabolites, angiogenesis inhibitors, fluorescence imaging, mass spectrometry imaging, tumor necrosis, rabbit model
MeSH terms
Sunitinib, Animals, Disease Models, Animal, Liver, Liver Neoplasms, Microspheres, Rabbits, Mass Spectrometry, Drug Delivery Systems, Angiogenesis Inhibitors, Cell Line, Tumor, Optical Imaging

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