TY - JOUR T1 - Molecular Imaging with Macrophage CRIg-Targeting Nanobodies for Early and Preclinical Diagnosis in a Mouse Model of Rheumatoid Arthritis JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 824 LP - 829 DO - 10.2967/jnumed.113.130617 VL - 55 IS - 5 AU - Fang Zheng AU - Stéphanie Put AU - Luc Bouwens AU - Tony Lahoutte AU - Patrick Matthys AU - Serge Muyldermans AU - Patrick De Baetselier AU - Nick Devoogdt AU - Geert Raes AU - Steve Schoonooghe Y1 - 2014/05/01 UR - http://jnm.snmjournals.org/content/55/5/824.abstract N2 - 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 (Nanobodies). Methods: Quantitative polymerase chain reaction 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-positive cells. SPECT (SPECT/CT) was used to image arthritic lesions in the inflamed paws of 29 mice using 99mTc-NbV4m119 Nanobody. 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-positive liver macrophages in naïve wild-type but not in CRIg−/− (CRIg knockout) mice. In CIA mice, 99mTc-NbV4m119 accumulation in arthritic lesions increased according to the severity of the inflammation. In the 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. ER -