Molecular Imaging with Macrophage CRIg-Targeting Nanobodies for Early and Preclinical Diagnosis in a Mouse Model of Rheumatoid Arthritis

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Samenvatting

An accurate and noninvasive tracer able to detect molecular events underlying the development of rheumatoid arthritis (RA) would be useful for RA diagnosis and drug efficacy assessment. A complement receptor of the Ig superfamily (CRIg) is expressed on synovial macrophages of RA patients, making it an interesting target for molecular imaging of RA. We aim to develop a radiotracer for the visualization of CRIg in a mouse model for RA using radiolabeled single domain variable antibody VHH fragments (a.k.a. Nanobodies).
METHODS qPCR was used to locate CRIg expression in mice with collagen-induced arthritis (CIA). A Nanobody, NbV4m119, was generated to specifically target CRIg. Flow cytometry, phosphorimaging and confocal microscopy were used to confirm NbVm119 binding to CRIg+ cells. Single-photon emission computed tomography (SPECT/CT) was used to image arthritic lesions in the inflamed paws of 29 mice using the 99mTc-NbV4m119 Nb.
RESULTS CRIg is constitutively expressed in the liver and was found to be upregulated in synovial tissues of CIA mice. SPECT/CT imaging revealed that 99mTc-NbV4m119 specifically targeted CRIg+ liver macrophages in naïve wild type but not in CRIg-/- mice. In CIA mice, 99mTc-NbV4m119 accumulation in arthritic lesions increased according to the severity of the inflammation. In knees of mice with CIA, 99mTc-NbV4m119 was found to accumulate even before the onset of macroscopic clinical symptoms.
CONCLUSION SPECT/CT imaging with 99mTc-NbV4m119 visualizes joint inflammation in CIA. Furthermore, imaging could predict which mice will develop clinical symptoms during CIA. Consequently, imaging of joint inflammation with CRIg-specific Nanobodies offers perspectives for clinical applications in RA patients.
Originele taal-2English
Pagina's (van-tot)824-829
Aantal pagina's6
TijdschriftJournal of Nuclear Medicine
Volume55
Nummer van het tijdschrift5
StatusPublished - 1 mei 2014

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