This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Research in tumor angiogenesis often relies on tumor bearing animal models; thus understanding the angiogenic behavior, and the contribution of the microenvironment to tumor progression is critical. In this study, tumor growth in both xenograph and syngeneic mouse models was characterized using MRI to validate the hypothesis that the host environment can significantly alter the vascularization of human cancer cells grown in mouse model. Methods and Discussion: Xenograph model was used with human glioblastoma U87 cells, and sygeneic model was used with murine glioma GL261 or murine squamous cell carcinoma VII cells implanted subcutaneously in the rear flank of mice. Animals were imaged at 1.5T MRI starting when the tumors reached a diameter of about 5 mm. T1 (spin-echo) and T2 (fast spin-echo) weighted images were acquired pre- and post- contrast agent Gd(DTPA) administration. T1- and T2-wt MR contrast-enhancing and non-enhancing imaging features were used to characterize tumors to differential temporal stages. Histological staining was used to characterize the pathological features of these tumors. Tumors in the xenograph model reached 5 mm in diameter about 4 weeks after tumor implantation. Post-contrast T1- and T2-wt MR images were homogeneous throughout the tumors (Stage 1). Tumors progressed to Stage 2 and last for 3-5 days, with a rim-enhanced post-contrast T1-wt and a homogeneous T2-wt MR patterns. These features correspond to an increasing activity of vascularization on the periphery of viable tumors. Tumors progress to Stage 3 by week 5, with an elevated T2-wt signal at the area with no enhancement in the post-contrast T1-wt images. These features correlate with the development of the necrosis. The results were confirmed by histological staining. Tumors in the sygeneic model reached Stage 1 with MR imaging patterns as described above about 2-3 weeks after tumor implantation; Stage 2 at about 3-5 weeks; and Stage 3 at about 5 weeks. Three differential observations were identified between the xenograph and syngeneic models: (1) Initial rate of tumor growth is much delayed in xenograph model; (2) The absolute MR intensity in the homogeneous post-contrast T1 image associated with Stage 1 is brighter in the xenograph model; (3) Stage 2 tumor progression in xenograph model was extremely short. The results were also confirmed by histological staining.
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