SIR 2024
Interventional Oncology
Luke R. Wilkins, MD, FSIR
Associate Professor
University of Virginia
Financial relationships: Full list of relationships is listed on the CME information page.
Vishnu M. Chandra, MD
IR Resident
University of Virginia
Financial relationships: Full list of relationships is listed on the CME information page.
Claire Carter, PhD
Associate Professor
Hackensack Meridian School of Medicine
Disclosure information not submitted.
Annapurna Pamreddy, PhD
Associate Professor
Hackensack Meridian School of Medicine
Disclosure information not submitted.
Four woodchucks with HCC resulting from hepatitis infection were divided into 2 groups: CA drug-eluting beads (CA-DEB) (n=2, LC-beads with bound CA) and standard doxorubicin DEB (DOX-DEB) (n=2). Embolization to angiographic stasis was performed through a microcatheter at the segmental level. Animals were euthanized at 1 and 4 hrs, livers harvested, and tumors flash frozen. Liver samples were cryosectioned at 10 µm. Mass spectrometry imaging (MSI) data were acquired using a Bruker SolariX 2xR FT-ICR mass spectrometer equipped with a dual ESI/MALDI ion source and Smartbeam II Nd:YAG (355 nm) laser. Following data acquisition, the slides were washed and stained with H&E according to the manufacturer protocol. Data were processed using FlexImaging and the SCiLs lab software. The ion maps of caffiec acid and doxorubicin were directly overlaid with their corresponding H&E stained sections for data analysis and co-registration of drug distribution with pathology.
Results:
MSI of DOX-DEB within HCC liver sections demonstrated minimal dispersion and penetration into the tumor microenvironment at both 1 and 4 hours post-TACE. At 1hr post-TACE, doxorubicin did not penetrate >300 µm from the edge of beads. At 4hrs post-TACE, doxorubicin did not penetrate >500 µm from the edge of the outer most bead.
MSI of CA-DEB showed dispersion of CA throughout the tumor microenvironment with higher accumulation detected within specific lobules at both 1 and 4 hrs. At 1hr post-CA-DEB, CA was detected throughout the visualized tumor specimen in a uniform distribution. At 4hrs post-CA-DEB, CA was detected heterogeneously through visualized sample. Both time points showed more uniform distribution of CA throughout the analyzed tumor section when compared with DOX-DEB.
Conclusion:
In vivo drug distribution in the tumor microenvironment can be successfully measured using MALDI. Results showed minimal release and distribution of drug from DOX-DEB versus more uniform distribution of CA from DEB at tumoricidal concentrations.