Korean J Radiol.  2012 Aug;13(4):450-457. 10.3348/kjr.2012.13.4.450.

Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data

• Cha JH
• Lee SH
• Lee SW
• Park K
• Moon DH
• Kim K
• Biswal S

• KMID: 1383857
• DOI: http://doi.org/10.3348/kjr.2012.13.4.450

Abstract

OBJECTIVE
To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA).
MATERIALS AND METHODS
We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 microL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice.
RESULTS
The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 +/- 0.76 and 0.79 +/- 0.71, respectively, for CIA mice; and 0.57 +/- 0.17 and 0.54 +/- 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 +/- 1.54 x 10(5) and 2.75 +/- 1.51 x 10(5), respectively, for CIA mice, and 1.22 +/- 0.27 x 10(5) and 0.88 +/- 0.24 x 10(5), respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice.
CONCLUSION
NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis.

Keyword

HGC-Cy5.5; 18F-FDG PET; Near-infrared fluorescence imaging; Rheumatoid arthritis

MeSH Terms

Animals
Ankle Joint/radionuclide imaging
Arthritis, Experimental/*radionuclide imaging
Carbocyanines/administration & dosage/*diagnostic use
Chitosan/administration & dosage/*diagnostic use
Fluorodeoxyglucose F18/administration & dosage/diagnostic use
Injections, Intravenous
Knee Joint/radionuclide imaging
Male
Mice
Microscopy, Confocal
Nanoparticles
Positron-Emission Tomography/*methods
Radiopharmaceuticals/administration & dosage/diagnostic use
Statistics, Nonparametric

Figure

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  Fig. 1 Chemical structures and in this study. A. Chemical structure of Cyanine 5.5-labeled hydrophobically modified glycol chitosan (HGC-Cy5.5) conjugates. B. Chemical structure of cyanine 5.5. C. Schematic diagram of HGC-Cy5.5 nanoparticles

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  Fig. 2 Transmission electron microscopy images of hydrophobically modified glycol chitosan nanoparticles.

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  Fig. 3 Time intensity curve for mean photon counts of cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles in collagen-induced arthritis mice.

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  Fig. 4 Diagrams showing results of this study. Results of 18F-fluorodeoxyglucose-micro positron emission tomography uptake in knee joint (A) and ankle joint (B). Near infrared fluorescence uptake in knee joint (C) and ankle joint (D).

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  Fig. 5 Results of 18F-fluorodeoxyglucose-micro positron emission tomography imaging (A) and near-infrared fluorescence imaging (B) using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles at knees (arrows) and ankles (arrowheads) in normal mice.

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  Fig. 6 Results of 18F-fluorodeoxyglucose-micro positron emission tomography imaging (A) and near-infrared fluorescence imaging (B) using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles at knees (arrows) and ankles (arrowheads) in collagen-induced arthritis mice.

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  Fig. 7 Confocal laser scanning microscopy of arthritic knee (A) and control knee (B), showing that cyanine 5.5-conjugated, hydrophobically modified, glycol chitosan nanoparticles emit bright red light (arrows) at synovial and subsynovial layers of arthritic knees (× 400 magnification).

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