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Abstract

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 receptortargeted 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.

Optical tomographic imaging discriminates between disease-modifying anti-rheumatic drug (DMARD) and non-DMARD efficacy in collagen antibody-induced arthritis

“…In this study, intravenous injection of a cathepsin-activatable agent, ProSense750, allowed the detection of activated inflammatory cells (for example, monocytes, lymphocytes) within the joints and paws of arthritic mice, confirming the findings of other researchers using only semiquantitative two-dimensional surface FRI imaging [33,36,39]. We built upon these earlier observations by assessing three-dimensional FMT imaging and quantification of arthritic mouse paws (in units of picomoles rather than relative fluorescence units), revealing quantitative 30-fold to 40-fold increases in the level of fluorescent signal as compared with control mice (Figure 5a, b).…”

Development of optical probes for in vivo imaging of polarized macrophages during foreign body reactions

“…This indicates that even when all appropriate steps are taken, the possibility of infection remains high and should be regarded with concern. It is well established that LPS prompts a localized inflammatory response with the increased accumulation of inflammatory cells and mediators including activated MΦ [55-57]. Similarly, pathogens, including Staphylococcus aureus bacteria, are known to induce a range of activation profiles for MΦ priming the cells to mount an immune response [58].…”

The Targeting Behavior of Folate-Nanohydrogel Evaluated by Near Infrared Imaging System in Tumor-Bearing Mouse Model

“…The targeting behavior of folate or folate-conjugate for FR expressing tumor cells was definite and extensively used as a functional ligand in tumor targeting researches (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In this study, folate-NHG showed good targeting capability in all three FR positive tumor models (HeLa, SMMC-7721 and Bel-7402) with different sizes.…”

“…Since the FR-mediated endocytosis was first discovered by Philip S. Low and Christopher P. Leamon in Purdue University in 1991, folate has been widely used as an optimal targeting ligand for selective delivery of attached drugs or macromolecular carriers to tumors (15). More and more folate conjugations have been developed and used in tumor treatment and imaging, such as polymeric carriers (10)(11)(12) and small imaging or therapeutic agents (16)(17)(18)(19)(20)(21). At least four folateconjugated drugs/prodrugs ( 111 In-DTPA-folate, EC17, EC20 and EC145), designed by Philip S. Low and Christopher P. Leamon, have entered human clinical trials (22).…”