Premium
MR angiogenesis imaging with Robo4‐ vs . α V β 3 ‐targeted nanoparticles in a B16/F10 mouse melanoma model
Author(s) -
Boles Kent S.,
Schmieder Anne H.,
Koch Alexander W.,
Carano Richard A. D.,
Wu Yan,
Caruthers Shelton D.,
Tong Raymond K.,
Stawicki Scott,
Hu Grace,
Scott Michael J.,
Zhang Huiying,
Reynolds Benton A.,
Wickline Samuel A.,
Lanza Gregory M.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-157933
Subject(s) - magnetic resonance imaging , angiogenesis , integrin , cancer research , melanoma , cancer , pathology , biology , medicine , cell , radiology , genetics
The primary objective of this study was to utilize MR molecular imaging to compare the 3‐dimensional spatial distribution of Robo4 and α V β 3 ‐integrin as biosignatures of angiogenesis, in a rapidly growing, syngeneic tumor. B16‐F10 melanoma‐bearing mice were imaged with magnetic resonance (MR; 3.0 T) 11 d postimplantation before and after intravenous administration of either Robo4‐ or α V β 3 ‐targeted paramagnetic nanoparticles. The percentage of MR signal‐enhanced voxels throughout the tumor volume was low and increased in animals receiving α V β 3 ‐ and Robo4‐targeted nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery ( i.e ., outer 50% of volume). Microscopic examination of tumors coexposed to the Robo4‐ and α V β 3 ‐targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with α V β 3 ‐integrin. Robo4‐ and α V β 3 ‐targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that α V β 3 ‐integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but α V β 3 ‐integrin expression was more detectable by MR at 3.0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with α V β 3 ‐integrin expression, may help define tumor character prior to and following cancer therapy.—Boles, K. S., Schmieder, A. H., Koch, A. W., Carano, R. A. D., Wu, Y., Caruthers, S. D., Tong, R. K., Stawicki, S., Hu, G., Scott, M. J., Zhang, H., Reynolds, B. A., Wickline, S. A., and Lanza, G. M. MR angiogenesis imaging with Robo4‐ vs . α V β 3 ‐targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB J . 24, 4262–4270 (2010). www.fasebj.org