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

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.ProceduresA431 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 (1mg/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.ResultsGenistein 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.ConclusionsAs 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.

Recent Advances in Nanotechnology-Based Targeted Delivery Systems of Active Constituents in Natural Medicines for Cancer Treatment

“…A large number of natural products have potent anti-tumor activities and are under preclinical studies. For example, genistein had a powerful therapeutic effect in vivo on A431 and Colo205 tumor-bearing mice [212]. De Oliveira et al [213] selected 18 studies (116 animals) for meta-analysis.…”

Anti‑chondrocyte apoptosis effect of genistein in treating inflammation‑induced osteoarthritis

“…Moreover, estrogen regulates chondrocyte metabolism in the treatment of OA by inhibiting the release of MMPs and promoting cartilage matrix formation ( 40 ). Genistein, which is the main component of isoflavone extracted from soybean, has antitumor, neuroprotective, bone metabolism-regulating, anti-osteoporosis, anti-inflammatory and antioxidant effects ( 41 – 43 ).…”

Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft

“…It should be noted here that there have been several reports on PET studies using [ 18 F]FLT and rodents [34, 35]. Honndorf et al [34] monitored the impact of genistein therapy using the two PET tracers [ 18 F]FDG and [ 18 F]FLT in vivo in two xenograft mouse models.…”

“…Honndorf et al [34] monitored the impact of genistein therapy using the two PET tracers [ 18 F]FDG and [ 18 F]FLT in vivo in two xenograft mouse models. Rapic et al [35] investigated the early effects of chemotherapeutic treatment on cancer cell proliferation in a BRAF-mutated colorectal cancer using [ 18 F]FLT.…”