Author(s): Cheng V.W.T.; Soto M.S.; Khrapitchev A.A.; Perez-Balderas F.; Sibson N.R.; Zakaria R.; Jenkinson M.D.; Middleton M.R.
Source: Clinical Cancer Research; Jan 2019; vol. 25 (no. 2); p. 533-543
Publication Date: Jan 2019
Publication Type(s): Article
Abstract:Purpose: A major issue for the effective treatment of brain upregulation across the time course. T2-weighted MRI of metastasis is the late stage of diagnosis with existing clinical all tumor-bearing mice injected with VCAM-MPIO showed tools. The aim of this study was to evaluate the potential of significantly more signal hypointensities (P < 0.001; two-vascular cell adhesion molecule 1 (VCAM-1)-targeted MRI for sided) than control cohorts, despite a lack of blood-brain early detection of brain micrometastases in mouse models barrier (BBB) impairment. Specific MPIO binding to across multiple primary tumor types. VCAM-1-positive tumor-associated vessels was confirmed Experimental Design: Xenograft models of brain microme-histologically. VCAM-1 expression was demonstrated in tastasis for human breast carcinoma (MDA231Br-GFP), lung human brain metastasis samples, across all three primary adenocarcinoma (SEBTA-001), and melanoma (H1_DL2) tumor types. were established via intracardiac injection in mice. Animals Conclusion(s): VCAM-1-targeted MRI enables the detec-(n 1/4 5-6/group) were injected intravenously with VCAM-1-tion of brain micrometastases from the three primary targeted microparticles of iron oxide (VCAM-MPIO) and, tumor types known to cause the majority of clinical cases. subsequently, underwent T2-weighted MRI. Control groups These findings represent an important step forward in of nave mice injected with VCAM-MPIO and tumor-bearing the development of a broadly applicable and clinically mice injected with nontargeting IgG-MPIO were included. relevant imaging technique for early diagnosis of brain Results: All models showed disseminated micrometas-metastasis, with significant implications for improved tases in the brain, together with endothelial VCAM-1 patient survival.
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