Chris Bull, Sr. Scientific Advisor, Imaging


July 2016

Brain metastases are the most common type of brain tumors, with the total number diagnosed annually outnumbering all other intracranial tumors combined. With the increasing survival of patients with primary disease, the incidence of the most common metastatic cancers (lung, breast, melanoma, renal, and colon) is thought to be rising.1 The frequency of brain metastases in patients dying from cancer varies from 20 to 50%.

A clinical standard in oncology, Dynamic Contrast Enhancement (DCE) MRI allows the quantification of spatially-resolved parameters that are measures of tumor permeability, blood flow, and vascular surface area. The protocol is based on systemic administration of a bolus of a gadolinium-containing contrast molecule, then tracking its extravasation over time. Clinically this technique follows treatment effects on brain metastasis longitudinally.

Fig. 1a:  Gadolinium DCE-MRI Longitudinal Image

Fig. 1a: Gadolinium DCE-MRI Longitudinal Image

Fig. 1b:  Gadolinium DCE-MRI Concentration Curve

Fig. 1b: Gadolinium DCE-MRI Concentration Curve

Utilization of orthotopic models of brain metastasis can significantly contribute to our understanding of the molecular mechanisms that occur during the final stages of metastatic growth in the brain and they should, therefore, be well suited for the study of new therapies.2 At Covance, we have implanted the human, non-small cell lung cancer line NCI-H2228 into the brain of NOD SCID mice and applied the clinically translatable DCE MRI technique. We find that this tumor line grows well in the brain and with DCE MRI are able to track blood flow and permeability of the tumor tissue, represented here as Ktrans (see Fig. 1a and 1b). This data is highly quantifiable and can be monitored over time to evaluate treatment effects on the same tumor (Fig 2). Utilization of this technique preclinically could have great impact when targeting angiogenesis or in evaluating the disruption of the blood brain barrier.

Our DCE MRI protocol was optimized in collaboration with industry pioneers. Thus, our acquisition and analysis procedures provide maximal clinical relevance, data reproducibility, and efficiency. The applicability of this technique spans a broad range of subcutaneous and orthotopic tumor models. Contact Covance today to speak with one of our imaging scientists to find out how you can apply DCE MRI to your preclinical oncology work.

Fig. 2:  K-trans Values Over Time

Fig. 2: K-trans Values Over Time

1K Stelzer. Epidemiology and prognosis of brain metastases. Surg Neurol Int. 2013 4(suppl 4): S192-S202.

2I Daphu,T Sundstrøm, S Horn, P Huszthy, S Niclou, P Sakariassen, H Immervoll, H Miletic, R Bjerkvig, Frits Thorsen.  In vivo animal models for studying brain metastasis: value and limitations.  Clin Exp Metastasis. 30 (5). 2013.

Note: Studies were performed in accordance with applicable animal welfare regulations in an AAALAC-accredited facility