Abstract
PurposeHypoxia is linked to aggressiveness, resistance to therapy, and poor prognosis of pancreatic tumors. Liposomal irinotecan (nal-IRI, ONIVYDE®) has shown potential in reducing hypoxia in the HT29 colorectal cancer model, and here, we investigate its therapeutic activity and ability to modulate hypoxia in patient-derived orthotopic tumor models of pancreatic cancer.ProceduresMice were randomized into nal-IRI treated and untreated controls. Magnetic resonance imaging was used for monitoring treatment efficacy, positron emission tomography (PET) imaging with F-18-labelled fluoroazomycinarabinoside ([18F]FAZA) for tumor hypoxia quantification, and F-18-labelled fluorothymidine ([18F]FLT) for tumor cell proliferation.ResultsThe highly hypoxic OCIP51 tumors showed significant response following nal-IRI treatment compared with the less hypoxic OCIP19 tumors. [18F]FAZA-PET detected significant hypoxia reduction in treated OCIP51 tumors, 8 days before significant changes in tumor volume. OCIP19 tumors also responded to therapy, although tumor volume control was not accompanied by any reduction in [18F]FAZA uptake. In both models, no differences were observable in [18F]FLT uptake in treated tumors compared with control mice.ConclusionsHypoxia modulation may play a role in nal-IRI’s mechanism of action. Nal-IRI demonstrated greater anti-tumor activity in the more aggressive and hypoxic tumor model. Furthermore, hypoxia imaging provided early prediction of treatment response.
Highlights
Pancreatic cancer is the third leading cause of cancer-related death in the USA [1], and its incidence rates are continuously increasing [2, 3]
Some chemotherapy agents have shown the capability to modulate hypoxia [24]. Among those is liposomal irinotecan, currently approved in North America, Europe, and select Asia-Pacific countries in combination with fluorouracil and leucovorin for the treatment of patients with advanced metastatic pancreatic cancer after disease progression following gemcitabine-based therapy [25], a tumor indication characterized by low vascular density as well as numerous and pronounced hypoxic regions [26]
We explore the value of longitudinal [18F]FAZA-positron emission tomography (PET) imaging in two orthotopic patient-derived xenograft (PDX) models of pancreatic cancer with low (OCIP19) and high hypoxia (OCIP51), following treatment with nal-IRI
Summary
Pancreatic cancer is the third leading cause of cancer-related death in the USA [1], and its incidence rates are continuously increasing [2, 3]. Some chemotherapy agents have shown the capability to modulate hypoxia [24] Among those is liposomal irinotecan (nal-IRI, ONIVYDE®, irinotecan liposome injection, MM398), currently approved in North America, Europe, and select Asia-Pacific countries in combination with fluorouracil and leucovorin for the treatment of patients with advanced metastatic pancreatic cancer after disease progression following gemcitabine-based therapy [25], a tumor indication characterized by low vascular density as well as numerous and pronounced hypoxic regions [26]. We explore the value of longitudinal [18F]FAZA-PET imaging in two orthotopic patient-derived xenograft (PDX) models of pancreatic cancer with low (OCIP19) and high hypoxia (OCIP51), following treatment with nal-IRI The goal of this investigation is to evaluate both the therapeutic activity of nal-IRI in orthotopic pancreatic cancer models and to assess its ability to modulate hypoxia changes in tumors that have inherently high or low baseline hypoxia levels. The goal of this investigation is to evaluate both the therapeutic activity of nal-IRI in orthotopic pancreatic cancer models and to assess its ability to modulate hypoxia changes in tumors that have inherently high or low baseline hypoxia levels. [18F]FLT-PET imaging was employed to track changes in tumor cell proliferation following nal-IRI therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
