Detection of dysplastic intestinal adenomas using a fluorescent folate imaging probe.
Macrophages have long been recognized as a prominent component of tumors. Activated macrophages overexpress folate receptors and we used this phenomenon to image inflammatory reactions in colon dysplasia using a fluorescent folate probe (FFP). APC(Delta468) mice injected with FFP showed fluorescent adenomas (target-to-background ratio, adenoma vs. adjacent normal mucosa, of 2.46 +/- 0.41), significantly higher (p < .001) than adenomas in animals injected with a non-folate-containing control probe. Fluorescence-activated cell-sorting analysis revealed a 3-fold higher content of Mac1-positive cells in colonic adenomas compared with normal adjacent mucosa (6.8% vs. 2.2%), and confirmed the source of FFP-positive cells to be primarily an F4/80-positive macrophage subpopulation. Taken together, these results indicate that probe potentially can be used to image dysplastic intestinal adenomas in vivo.
Chen
Wei-Tsung
WT
Center for Molecular Imaging Research, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 92129, USA.
Khazaie
Khashayarsha
K
Zhang
Guoying
G
Weissleder
Ralph
R
Tung
Ching-Hsuan
CH
D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods*; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000032:analysis*; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D011956:Receptors, Cell Surface / Q000378:metabolism
D000943:Antigens, Differentiation; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D016177:Macrophage-1 Antigen; D011956:Receptors, Cell Surface; C036763:monocyte-macrophage differentiation antigen; D005492:Folic Acid