Use of non-invasive imaging to monitor response to aflibercept treatment in murine models of colorectal cancer liver metastases.
The liver is the most frequent metastatic site in colorectal cancer (CRC), and relevant orthotopic in vivo models are needed to study the efficacy of anticancer drugs in the metastatic setting. A challenge when utilizing such models is monitoring tumor growth during the experiments. In this study, experimental liver metastases were established in nude mice by splenic injection of the CRC cell lines HT29 and HCT116, and the mice were treated with the antiangiogenic drug aflibercept. Tumor growth was monitored using magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). Aflibercept treatment was well tolerated and resulted in increased animal survival in HCT116, but not in HT29, while inhibited tumor growth was observed in both models. Treatment efficacy was monitored with high precision using MRI, while BLI detected small-volume disease with high sensitivity, but was less accurate in end-stage disease. Apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DW-MRI) were highly predictive of treatment response, with increased ADC corresponding well with areas of necrosis observed by histological evaluation of aflibercept-treated xenografts. The results showed that the efficacy of the antiangiogenic drug aflibercept varied between the two models, possibly reflecting unique growth patterns in the liver that may be representative of human disease. Non-invasive imaging, especially MRI and DW-MRI, can be used to effectively monitor tumor growth and treatment response in orthotopic liver metastasis models.
Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
Karianne G
0000-0003-0697-9750
KG
Fleten
Department of Oncology, Akershus University Hospital, Lørenskog, Norway.|Department of Physics, University of Oslo, Oslo, Norway.
Kine M
KM
Bakke
Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310, Oslo, Norway.|Department of Pharmacy, University of Tromsø, Tromsø, Norway.
Gunhild M
GM
Mælandsmo
Department of Radiology and Nuclear Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
Andreas
A
Abildgaard
Department of Oncology, Akershus University Hospital, Lørenskog, Norway.
Kathrine Røe
KR
Redalen
Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310, Oslo, Norway. kjersti.flatmark@rr-research.no.|Faculty of Medicine, University of Oslo, Oslo, Norway. kjersti.flatmark@rr-research.no.|Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. kjersti.flatmark@rr-research.no.
Kjersti
K
Flatmark
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor
Aflibercept; Colorectal cancer; In vivo models; Liver metastasis; Non-invasive imaging