Oncotarget

Research Papers:

Preclinical evaluation of the anti-tumor effects of the natural isoflavone genistein in two xenograft mouse models monitored by [18F]FDG, [18F]FLT, and [64Cu]NODAGA-cetuximab small animal PET

Valerie S. Honndorf _, Stefan Wiehr, Anna-Maria Rolle, Julia Schmitt, Luisa Kreft, Letitia Quintanilla-Martinez, Ursula Kohlhofer, Gerald Reischl, Andreas Maurer, Karsten Boldt, Michael Schwarz, Holger Schmidt and Bernd J. Pichler

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Oncotarget. 2016; 7:28247-28261. https://doi.org/10.18632/oncotarget.8625

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Abstract

Valerie S. Honndorf1, Stefan Wiehr1, Anna-Maria Rolle1, Julia Schmitt1, Luisa Kreft1, Letitia Quintanilla-Martinez2, Ursula Kohlhofer2, Gerald Reischl1, Andreas Maurer1, Karsten Boldt3, Michael Schwarz4, Holger Schmidt5, Bernd J. Pichler1

1Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany

2Institute of Pathology, University Hospital, Eberhard Karls University, Tuebingen, Germany

3Medical Proteome Center, Institute for Ophthalmic Research, Eberhard Karls University, Tuebingen, Germany

4Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, Eberhard Karls University, Tuebingen, Germany

5Department of Radiology, Diagnostic and Interventional Radiology, Eberhard Karls University, Tuebingen, Germany

Correspondence to:

Valerie S. Honndorf, email: [email protected]

Keywords: PET, genistein and cetuximab, A431 and Colo205 xenografts, molecular tumor imaging

Received: December 21, 2015     Accepted: February 28, 2016     Published: April 07, 2016

ABSTRACT

The natural phytoestrogen genistein is known as protein kinase inhibitor and tumor suppressor in various types of cancers. We studied its antitumor effect in two different xenograft models using positron emission tomography (PET) in vivo combined with ex vivo histology and nuclear magnetic resonance (NMR) metabolic fingerprinting.

Procedures: A431 and Colo205 tumor-bearing mice were treated with vehicle or genistein (500 mg/kg/d) over a period of 12 days. Imaging was performed with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3′-deoxy-3′-[18F]fluorothymidine ([18F] FLT). In a second study A431 tumor-bearing mice were treated with vehicle, genistein (500 mg/kg/d), cetuximab (1 mg/3d) or a combination of the compounds and imaged using [18F]FDG, [18F]FLT and [64Cu]NODAGA-cetuximab. Data were compared to histology and principal components analysis (PCA) of NMR fingerprinting data.

Results: Genistein reduced tumor growth significantly in both xenografts. [18F] FLT uptake was consistent in both models and corresponded to histological findings and also PCA whereas [18F]FDG and [64Cu]NODAGA-cetuximab were not suitable for therapy monitoring.

Conclusions: As mono-therapy the natural isoflavone genistein has a powerful therapeutic effect in vivo on A431 and Colo205 tumors. [18F]FLT has superior consistency compared to the other tested tracers in therapy monitoring, while the treatment effect could be shown on the molecular level by histology and metabolic fingerprinting.


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