Dynamic ¹⁸F-FDG-PET for monitoring treatment effect following anti-angiogenic therapy in triple-negative breast cancer xenografts

Abstract

Introduction. Dynamic ¹⁸F-FDG PET allows the study of glucose distribution in tissues as a function of time and space. Using pharmacokinetics, the temporal uptake pattern of ¹⁸F-FDG may be separated into components reflecting perfusion and metabolism. Bevacizumab is an angiogenesis inhibitor which prevents the growth of new blood vessels, and may potentially lead to normalization of the blood circulation in the tumor. The purpose of the study was to explore the use of dynamic PET as a tool for monitoring treatment effect, reflected by changes in perfusion and metabolism. Materials and Methods. Twelve athymic nude mice, bearing the bilateral triple-negative human breast cancer xenograft MAS98.12 were treated with bevacizumab (5 mg/kg i.p.). Dynamic PET data was acquired prior to and 24 and 72 hours after treatment for 1 hour after injection of 10 MBq ¹⁸F-FDG and fitted with a FDG two-tissue compartment model. The changes in the rate constants k1, k3, MRFDG and the vascular fraction νB were assessed. To evaluate the effect of treatment regimes, 30 mice, randomized in 5 groups, received either vehicle (0.9% NaCl), bevacizumab (5 mg/kg i.p.), doxorubicin (8 mg/kg i.v.) or bevacizumab and doxorubicin either together, or doxorubicin 24 hours after bevacizumab treatment. Tumor volume was measured twice a week. Results. The perfusion-related rate parameter k1 and the metabolic rate constant k3 decreased significantly 24 hours after treatment. This decrease was followed by an increase, albeit non-significant, at 72 hours post treatment. Doxorubicin given 24 hours after bevacizumab showed less antitumor effect compared to concomitant treatment. Conclusions. Dynamic PET can detect changes in tumor perfusion and metabolism following anti-angiogenic therapy in mouse xenograft models. Longitudinal dynamic PET, used to assess the efficacy of anti-angiogenic treatment, can identify the time frame of potential tumor vasculature re-normalization and allow optimal timing of supplementary therapy (radiation or chemotherapy).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Financial support received from the K.G. Jebsen center for Breast Cancer research, Oslo, Norway is gratefully acknowledged.

Notice of correction

The version of this article published online ahead of print on 29 Aug 2013 contained an error on page 1. The heading of the article should have read “Original article”, not Letter to the Editor. The abstract was also missing. The error has been corrected for this version.