Arthritis imaging using a near-infrared fluorescence folate-targeted probe.
A recently developed near-infrared fluorescence-labeled folate probe (NIR2-folate) was tested for in vivo imaging of arthritis using a lipopolysaccharide intra-articular injection model and a KRN transgenic mice serum induction mouse model. In the lipopolysaccharide injection model, the fluorescence signal intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between lipopolysaccharide-treated and control joints. The fluorescence signal intensity of the NIR2-folate probe at the inflammatory joints was found to be significantly higher than the control normal joints (up to 2.3-fold, P < 0.001). The NIR2-free dye injection group showed a persistent lower enhancement ratio than the NIR2-folate probe injection group. Excessive folic acid was also given to demonstrate a competitive effect with the NIR2-folate. In the KRN serum transfer model (n = 4), NIR2-folate was applied at different time points after serum transfer, and the inflamed joints could be detected as early as 30 hours after arthritogenic antibody transfer (1.8-fold increase in signal intensity). Fluorescence microscopy, histology, and immunohistochemistry validated the optical imaging results. We conclude that in vivo arthritis detection was feasible using a folate-targeted near-infrared fluorescence probe. This receptor-targeted imaging method may facilitate improved arthritis diagnosis and early assessment of the disease progress by providing an in vivo characterization of active macrophage status in inflammatory joint diseases.
Chen
Wei-Tsung
WT
Center of Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Mahmood
Umar
U
Weissleder
Ralph
R
Tung
Ching-Hsuan
CH
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis* / Q000378:metabolism; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005240:Feasibility Studies; D005456:Fluorescent Dyes / Q000032:analysis*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D013582:Synovial Fluid / Q000166:cytology
D002352:Carrier Proteins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D008070:Lipopolysaccharides; C506173:NIR2-folate; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D005492:Folic Acid
Radiology. 1999 Dec;213(3):866-70
10580968
Arthritis Rheum. 1999 Aug;42(8):1609-16
10446858
Invest Radiol. 2000 Aug;35(8):479-85
10946975
Cancer Res. 2000 Sep 1;60(17):4953-8
10987312
Photochem Photobiol. 2000 Sep;72(3):392-8
10989611
N Engl J Med. 2001 Mar 22;344(12):907-16
11259725
Nat Biotechnol. 2001 Apr;19(4):327-31
11283589
Nat Med. 2001 Jun;7(6):743-8
11385514
Gastroenterology. 2002 Feb;122(2):406-14
11832455
Immunity. 2002 Feb;16(2):157-68
11869678
Bioconjug Chem. 2002 May-Jun;13(3):605-10
12009952
Arthritis Rheum. 2002 Jul;46(7):1947-55
12124880
Chembiochem. 2002 Aug 2;3(8):784-6
12203978
J Immunol. 2002 Dec 1;169(11):6604-9
12444173
Nat Med. 2003 Jan;9(1):123-8
12514725
Bioconjug Chem. 2003 May-Jun;14(3):539-45
12757377
Arthritis Res Ther. 2003;5(5):210-3
12932279
Osteoarthritis Cartilage. 2004 Mar;12(3):239-44
14972341
Arthritis Rheum. 2004 Mar;50(3):961-7
15022340
Adv Drug Deliv Rev. 2004 Apr 29;56(8):1205-17
15094216
Arthritis Rheum. 2004 Aug;50(8):2459-65
15334458
Yale J Biol Med. 1965 Dec;38(3):241-56
5866671
J Leukoc Biol. 1985 Feb;37(2):121-36
3881546
Arthritis Rheum. 1985 Dec;28(12):1402-11
3910050
Am J Pathol. 1986 Feb;122(2):323-34
3511727
Arthritis Rheum. 1986 Sep;29(9):1122-30
3489469
J Exp Med. 1987 Jun 1;165(6):1688-702
3295108
N Engl J Med. 1988 Mar 24;318(12):747-52
3279314
J Biol Chem. 1988 Sep 25;263(27):13602-9
3417674
Arthritis Rheum. 1996 Jan;39(1):115-24
8546720
Annu Rev Nutr. 1996;16:501-21
8839936
Cell. 1996 Nov 29;87(5):811-22
8945509
J Rheumatol. 1999 Mar;26(3):717-9
10090189
Nat Biotechnol. 1999 Apr;17(4):375-8
10207887
Immunity. 1999 Apr;10(4):451-61
10229188
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2767-72
10706610