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0 项与 Collagen Medical LLC 相关的专利（医药）

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项与 Collagen Medical LLC 相关的文献（医药）

2024-04-01·International Journal of Radiation Oncology*Biology*Physics

Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe

Article

作者: Fintelmann, Florian J ; Saenger, Jonathan A ; Zhou, Iris Y ; Lanuti, Michael ; Hariri, Lida P ; Catana, Ciprian ; Crowley, Elizabeth ; Caravan, Peter ; Akam, Eman ; Esfahani, Shadi A ; Shuvaev, Sergey ; Montesi, Sydney B ; Abston, Eric ; Rotile, Nicholas J ; Arabasz, Grae ; Humblet, Valerie ; Khandekar, Melin

PURPOSERadiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI.METHODS AND MATERIALSUsing a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe ⁶⁸Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quantified via autoradiography. ⁶⁸Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects.RESULTSMurine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and ⁶⁸Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant ⁶⁸Ga-CBP8 uptake in areas of RILI and minimal background uptake.CONCLUSIONSThese findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.

2020-09-15·Clinical Cancer Research1区 · 医学

Fibrotic Response to Neoadjuvant Therapy Predicts Survival in Pancreatic Cancer and Is Measurable with Collagen-Targeted Molecular MRI

1区 · 医学

Article

作者: Taylor, Martin S. ; Ferreira, Diego S. ; Deshpande, Vikram ; Jones, Chloe ; Humblet, Valerie ; Tanabe, Kenneth K. ; Chawla, Akhil ; Chen, Yin-Ching Iris ; Rotile, Nicholas J. ; Arora, Gunisha ; Ferrone, Cristina R. ; Farrar, Christian T. ; Li, Shen ; Ghoshal, Sarani ; Jordan, Veronica Clavijo ; Axtell, Andrea L. ; Fuchs, Bryan C. ; Kontos, Filippos ; Bardeesy, Nabeel ; Caravan, Peter ; Graham-O'Regan, Katherine A. ; Michelakos, Theodoros ; Sojoodi, Mozhdeh ; Qadan, Motaz ; Erstad, Derek J. ; Lanuti, Michael

AbstractPurpose: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.

Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe

作者: Hariri, Lida P ; Zhou, Iris Y ; Saenger, Jonathan A ; Fintelmann, Florian J ; Lanuti, Michael ; Caravan, Peter ; Humblet, Valerie ; Esfahani, Shadi A ; Shuvaev, Sergey ; Crowley, Elizabeth ; Akam, Eman ; Arabasz, Grae ; Rotile, Nicholas J ; Abston, Eric ; Montesi, Sydney B ; Catana, Ciprian

AbstractRationaleRadiation-induced lung injury (RILI) is a progressive inflammatory process commonly seen following irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management.ObjectiveTo noninvasively quantify RILI, utilizing a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI.MethodsUsing a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe to characterize the development of RILI and to assess disease mitigation following losartan treatment. The human analog probe targeted against type 1 collagen,68Ga-CBP8, was tested on excised human lung tissue containing RILI and quantified via autoradiography. Finally,68Ga-CBP8 PET was used to assess RILIin vivoin six human subjects.ResultsMurine models demonstrated that probe signal correlated with progressive RILI severity over six-months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding vs unirradiated control tissue and68Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant68Ga-CBP8 uptake in areas of RILI and minimal background uptake.ConclusionsThese findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.Clinical trial registered withwww.clinicaltrials.gov(NCT04485286,NCT03535545)

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