Methods for intratumoral microdialysis probe targeting and validation in murine brain tumor models

Karishma Rajani, Ian Olson, Joshua J. Jacobs, Cecile Riviere-cazaux, Kirsten Burns, Lucas Carlstrom, Mark Schroeder, Juhee Oh, Charles L. Howe, Masum Rahman, Jann N. Sarkaria, William F. Elmquist, Terry C. Burns

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Microdialysis is a well validated sampling technique that can be used for pharmacokinetic studies of oncological drugs targeting the central nervous system. This technique has also been applied to evaluate tumor metabolism and identify pharmacodynamic biomarkers of drug activity. Despite the potential utility of microdialysis for therapeutic discovery, variability in tumor size and location hamper routine use of microdialysis as a preclinical tool. Quantitative validation of microdialysis membrane location relative to radiographically evident tumor regions could facilitate rigorous preclinical studies. However, a widely accessible standardized workflow for preclinical catheter placement and validation is needed. New method: We provide methods for a workflow to yield tailored placement of microdialysis probes within a murine intracranial tumor and illustrate in an IDH1-mutant patient-derived xenograft (PDX) model. This detailed workflow uses a freely available on-line tool built within 3D-slicer freeware to target microdialysis probe placement within the tumor core and validate probe placement fully within the tumor. Results: We illustrate use of this workflow to validate microdialysis probe location relative to implanted IDH1-mutant PDXs, using the microdialysis probes to quantify levels of extracellular onco-metabolite D-2 hydroxyglutarate. Comparison with existing methods: Previous methods have used 3D slicer to reliably measure tumor volumes. Prior microdialysis studies have targeted expected tumor locations without validation. Conclusions: The new method offers a streamlined and freely available workflow in 3D slicer to optimize and validate microdialysis probe placement within a murine brain tumor.

Original languageEnglish (US)
Article number109321
JournalJournal of Neuroscience Methods
Volume363
DOIs
StatePublished - Nov 1 2021

Bibliographical note

Funding Information:
We thank Brett Carlson for his help with use of X-Rad. We also acknowledge the MRI, Division of Engineering, and Metabolomics cores at the Mayo Clinic. The authors have been supported by the following grants: Funding support (TCB) was supported by NIH K12 NRCDP, NINDS NS19770, the Minnesota Partnership for Biotechnology and Genomics, Mayo Clinic Center for Regenerative Medicine, Lucius & Terrie McKelvey, and Regenerative Medicine Minnesota.

Funding Information:
We thank Brett Carlson for his help with use of X-Rad. We also acknowledge the MRI, Division of Engineering, and Metabolomics cores at the Mayo Clinic. The authors have been supported by the following grants: Funding support (TCB) was supported by NIH K12 NRCDP , NINDS NS19770 , the Minnesota Partnership for Biotechnology and Genomics , Mayo Clinic Center for Regenerative Medicine , Lucius & Terrie McKelvey , and Regenerative Medicine Minnesota .

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • 2 hydroxyglutarate (2HG)
  • 3D slicer
  • Glioblastomas
  • Isocitrate dehydrogenase I (IDH-1)
  • Magnetic Resonance Imaging (MRI)
  • Microdialysis
  • Patient derived xenografts (PDX)

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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