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.

Abstract

UNLABELLED:

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.

• Authors: 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, Bernd J Pichler
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 19 Pg. 28247-61 (May 10 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27070087 (Publication Type: Journal Article)

Chemical References

• 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
• Acetates
• Anticarcinogenic Agents
• Copper Radioisotopes
• Copper-64
• Dideoxynucleosides
• Heterocyclic Compounds, 1-Ring
• Radioisotopes
• Fluorodeoxyglucose F18
• Genistein
• alovudine
• Cetuximab

Topics

• Acetates
• Animals
• Anticarcinogenic Agents (pharmacology)
• Cetuximab (pharmacology)
• Copper Radioisotopes
• Dideoxynucleosides
• Fluorodeoxyglucose F18
• Genistein (pharmacology)
• Heterocyclic Compounds, 1-Ring
• Humans
• Mice
• Mice, Nude
• Neoplasms, Experimental (diagnostic imaging, pathology)
• Positron-Emission Tomography (methods)
• Radioisotopes
• Xenograft Model Antitumor Assays