Angiogenesis process measurement

One of the obvious advantages of orthotopic models is that targeting processes involved in local invasion (e.g., angiogenesis) can be undertaken at a clinically relevant site (36). Since the early studies showing orthotopic transplantation of colon tumors and metastasis to the liver (39), tumor xenografts have been grown orthotopically in mice. However, despite the clinical relevance of orthotopic models, their utilization is hindered by a need for a high level of technical skill, time and cost. Therapeutic efficacy is also more difficult to assess with orthotopic models in contrast to the relative ease of subcutis tumor measurements (36). 

Molecular imaging has also been used to measure general processes such as angiogenesis, inflammation, hypoxia, or arteriosclerosis. As many diseases result in abnormalities of these processes (also named common denominators ), drug-based therapies aim at their modification. In other cases - such as the apoptosis of tumor cells - a change in this process is a desired therapeutic effect. For these reasons, quantitative measurement of the status of these processes may represent potential biomarkers of drug efficacy. 

Fig. 1. Microcirculation of a human colon carcinoma grown in the dorsal skin chamber in a severe-combined immunodeficient mouse. (Adapted from Leunig et al., 1992b.) Note that angiogenesis leads to formation of numerous blood vessels. Such a transparent preparation can permit noninvasive, continuous measurement of transport processes in normal and tumor tissues (Jain, 1985b). Parameters we can measure include hemodynamic (e.g., blood flow, vasomotion) metabolic (e.g., pH, p02, Ca2+) transport (e.g., permeability, diffusion, binding), and cell-cell interactions (e.g., adhesion, deformability).

---