RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 824
OP 829
DO 10.2967/jnumed.113.130617
VO 55
IS 5
A1 Fang Zheng
A1 Stéphanie Put
A1 Luc Bouwens
A1 Tony Lahoutte
A1 Patrick Matthys
A1 Serge Muyldermans
A1 Patrick De Baetselier
A1 Nick Devoogdt
A1 Geert Raes
A1 Steve Schoonooghe
YR 2014
UL http://jnm.snmjournals.org/content/55/5/824.abstract
AB 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.