A PARADIGM SHIFT IN CANCER THERAPY

Fortunately, advances in imaging technologies such as MRI, µCT and µPET not only enable measurement of anticancer activity by determination of tumor burden, but also provide mechanistic information at the level of the molecular target.

In addition, the ability to optimize compounds in vivo with imaging-derived pharmacodynamic profiles, prior to the determination of efficacy, can dramatically speed the cancer drug evaluation and drug discovery process by shortening turnaround times and reducing the amount of drug required. Finally, many of the imaging technologies proposed to evaluate drug function preclinically can be translated into a clinical benchmark with appropriate validation.

Studies using preclinical MRI imaging can provide detailed information on tumor size and heterogeneity (T1 and T2 weighted images), an early indication of therapeutic response (Diffusion MRI), tumor blood flow, blood volume, and vascular permeability (Arterial Spin Labeling and Dynamic Contrast Enhanced MRI) and other relevant parameters. MRI provides quantitative assessments of these and other parameters with high spatial resolution.

By tagging of cells or injectable molecules with fluorescent probes, or by use of transgenic animals that express genes for fluorescent proteins, tumor burden or cellular and molecular level interactions can be quantified. By simultaneous use of fluorescent labels in different regions of the light excitation or emission spectrum, multiple readouts can be obtained in a single experiment.

Angiogenesis is the formation of new blood micro-vessels from existing blood vessels.  This is one of the key requirements tumors require to obtain nutrients and oxygen and to become malignant.  Tumors release factors that actively promote angiogenesis.  These factors, such as VEGF, FGF, PGF, LEP, MDK and others, as well as the receptors they bind to have become promising therapeutic targets.  Other therapeutic targets are concerned with endothelial tube formation and tumor migration/invasion. Therapeutic agents to these targets have gained popularity in recent years and MIR has developed a program specifically for the preclinical evaluation of such agents.  In vitro services include cell migration, invasion and tube formation assays.  In vivo services include matrigel plug assays which is enhanced over traditional models, histology which looks at sections of human tumor xenografts stained with CD31 or Factor 8 and advanced imaging technologies such as dynamic contrast enhanced MRI (DCE MRI), a clinically translatable technology that can measure blood flow non-invasively in an animal in real time.  For more information, click on the link below.