Evaluation of treatment response of Cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET

Objectives Purpose of this study was the assessment of the feasibility of dynamic PET studies with FDG to quantify effects of Cilengitide, which targets the alpha-V/beta-3 and beta-5 integrin receptors in rats with breast cancer bone metastases.

Methods Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg after approximately 30 days. Rats were treated with Cilengitide (EMD 121974, Merck, Darmstadt, Germany) five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies were performed in untreated (n=9), controlled (n=4) and treated rats (n=7). The data were assessed using a two-tissue compartmental analysis.

Results The SUV, the tumor size and the FDG kinetic parameters showed significant differences when individual parameters were compared between groups. The phosphorylation rate k3 was significantly different between untreated and control group (p=0.023) and between control and treated animals (p=0.014). Moreover, significant differences were found in the tumor size between untreated and control animals (p=0.008), as well as between control and treated animals (p=0.006). Classification analysis based on SVM_RFE and PET parameters VB, K1, k3 and SUV revealed an overall accuracy of higher than 80.0% between groups. We were able to identify 100% untreated animals compared with control animals, and 100% treated animals compared with two other groups.

Conclusions The new quantitative method used within this study was helpful to assess the therapeutic effect. The results revealed that Cilengitide treatment on MDA-MB-231 breast cancer cells that have metastasized to bone had a significant impact on FDG kinetics, and k3 was most sensitive for therapeutic changes. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated limited effect of Cilengitide treatment on MDA-MB-231 breast cancer cells