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- Title
Non-Invasive Monitoring of Stromal Biophysics with Targeted Depletion of Hyaluronan in Pancreatic Ductal Adenocarcinoma.
- Authors
Maloney, Ezekiel; DuFort, Christopher C.; Provenzano, Paolo P.; Farr, Navid; Carlson, Markus A.; Vohra, Ravneet; Park, Joshua; Hingorani, Sunil R.; Lee, Donghoon
- Abstract
Pancreatic ductal adenocarcinoma (PDA) is characterized by a pronounced fibroinflammatory stromal reaction consisting of inordinate levels of hyaluronan (HA), collagen, immune cells, and activated fibroblasts that work in concert to generate a robust physical barrier to the perfusion and diffusion of small molecule therapeutics. The targeted depletion of hyaluronan with a PEGylated recombinant human hyaluronidase (PEGPH20) lowers interstitial gel–fluid pressures and re-expands collapsed intratumoral vasculature, improving the delivery of concurrently administered agents. Here we report a non-invasive means of assessing biophysical responses to stromal intervention with quantitative multiparametric magnetic resonance imaging (MRI) at 14 Tesla (T). We found that spin-spin relaxation time T2 values and glycosaminoglycan chemical exchange saturation transfer (GagCEST) values decreased at 24 h, reflecting depletion of intratumoral HA content, and that these parameters recovered at 7 days concurrent with replenishment of intratumoral HA. This was also reflected in an increase in low-b apparent diffusion coefficient (ADC) at 24 h, consistent with improved tumor perfusion that again normalized at 7 days after treatment. Phantom imaging suggests that the GagCEST signal is driven by changes in HA versus other glycosaminoglycans. Thus, multiparametric magnetic resonance imaging (MRI) can be used as a non-invasive tool to assess therapeutic responses to targeted stromal therapy in PDA and likely other stroma-rich solid tumors that have high levels of hyaluronan and collagen.
- Subjects
ADENOCARCINOMA; BIOPHYSICS; COLLAGEN; DIFFUSION; FIBROBLASTS; GLYCOSAMINOGLYCANS; HYALURONIC acid; MAGNETIC resonance imaging; PANCREATIC tumors; PERFUSION; IMAGING phantoms; DUCTAL carcinoma
- Publication
Cancers, 2019, Vol 11, Issue 6, p772
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11060772