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Open Access 03.09.2019 | Research Article

Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia

verfasst von: Manuela Ventura, Nicholas Bernards, Raquel De Souza, Inga B. Fricke, Bart S. Hendriks, Jonathan B. Fitzgerald, Helen Lee, Stephan G. Klinz, Jinzi Zheng

Erschienen in: Molecular Imaging and Biology | Ausgabe 3/2020

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Abstract

Purpose

Hypoxia 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.

Procedures

Mice 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.

Results

The 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.

Conclusions

Hypoxia 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.

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Titel: Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia
verfasst von: Manuela Ventura
Nicholas Bernards
Raquel De Souza
Inga B. Fricke
Bart S. Hendriks
Jonathan B. Fitzgerald
Helen Lee
Stephan G. Klinz
Jinzi Zheng
Publikationsdatum: 03.09.2019
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 3/2020
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-019-01374-x

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Longitudinal PET Imaging to Monitor Treatment Efficacy by Liposomal Irinotecan in Orthotopic Patient-Derived Pancreatic Tumor Models of High and Low Hypoxia