| Autor: |
Bryan C. Fuchs, Peter Caravan, Kenneth K. Tanabe, Michael Lanuti, Cristina R. Ferrone, Nabeel Bardeesy, Motaz Qadan, Vikram Deshpande, Valerie Humblet, Gunisha Arora, Yin-Ching Iris Chen, Sarani Ghoshal, Shen Li, Akhil Chawla, Filippos Kontos, Theodoros Michelakos, Diego S. Ferreira, Katherine A. Graham-O'Regan, Chloe Jones, Nicholas J. Rotile, Andrea L. Axtell, Christian T. Farrar, Veronica Clavijo Jordan, Martin S. Taylor, Mozhdeh Sojoodi, Derek J. Erstad |
| Rok vydání: |
2023 |
| Popis: |
Purpose:To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, to the standard contrast agent, Gd-DOTA, for their abilities to identify FOLFIRINOX-induced fibrosis in a murine model of PDAC.Experimental Design:Ninety-three chemoradiation-treated human PDAC samples were stained for fibrosis and outcomes evaluated. For imaging, C57BL/6 and FVB mice were orthotopically implanted with PDAC cells and FOLFIRINOX was administered. Mice were imaged with Gd-DOTA and CM-101.Results:In humans, post-chemoradiation PDAC tumor fibrosis was associated with longer overall survival (OS) and disease-free survival (DFS) on multivariable analysis (OS P = 0.028, DFS P = 0.047). CPA increased the prognostic accuracy of a multivariable logistic regression model comprised of previously established PDAC risk factors [AUC CPA (−) = 0.76, AUC CPA (+) = 0.82]. In multiple murine orthotopic PDAC models, FOLFIRINOX therapy reduced tumor weight (P < 0.05) and increased tumor fibrosis by collagen staining (P < 0.05). CM-101 MR signal was significantly increased in fibrotic tumor regions. CM-101 signal retention was also increased in the more fibrotic FOLFIRINOX-treated tumors compared with untreated controls (P = 0.027), consistent with selective probe binding to collagen. No treatment-related differences were observed with Gd-DOTA imaging.Conclusions:In humans, post-chemoradiation tumor fibrosis is associated with OS and DFS. In mice, our MR findings indicate that translation of collagen molecular MRI with CM-101 to humans might provide a novel imaging technique to monitor fibrotic response to therapy to assist with prognostication and disease management. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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