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

Zheng, Fang; Put, Stéphanie; Bouwens, Luc; Lahoutte, Tony; Matthys, Patrick; Muyldermans, Serge; Baetseĺier, Patrick De; Devoogdt, Nick; Raes, Geert; Schoonooghe, Steve

doi:10.2967/jnumed.113.130617

Cited by 51 publications

(46 citation statements)

References 33 publications

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“…Previous studies have focused mostly on targeting macrophages-either with radiolabeled folate (31)(32)(33), with (R)-11 C-PK11195 or translocator protein TSPO (34-36) (which has also been used clinically), or with radiolabeled nanobodies (37)-or by targeting CD163 receptors (38) or mannose receptors (39). Unfortunately, images acquired using radiolabeled folate led to poor-quality images (31), most probably due to general low uptake of the tracers in the joints (32), a feature also seen with the anti-CRIg Nanobody 99m Tc-NbV4m119 (37). So far, the only tool to image F4/80 receptors specifically has been near-infrared-labeled antibodies (40), making our radiolabeled anti-F4/80-A3-1 antibody a unique nuclear tool.…”

Section: Discussionmentioning

confidence: 99%

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

et al. 2015

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Rheumatoid arthritis is an autoimmune disease resulting in chronic synovial inflammation. Molecular imaging could be used to monitor therapy response, thus enabling tailored therapy regimens and enhancing therapeutic outcome. Here, we hypothesized that response to etanercept could be monitored by radionuclide imaging in arthritic mice. We tested 3 different targets, namely fibroblast activation protein (FAP), macrophages, and integrin α v β 3 . Methods: Male DBA/1J mice with collagen-induced arthritis were treated with etanercept. SPECT/ CT scans were acquired at 1, 24, and 48 h after injection of 111 In-RGD 2 (integrin α v β 3 ), 111 In-anti-F4/80-A3-1 (antimurine macrophage antibody), or 111 In-28H1 (anti-FAP antibody), respectively, with nonspecific controls included. Mice were dissected after the last scan, and scans were analyzed quantitatively and were correlated with macroscopic scoring. Results: Experimental arthritis was imaged with 111 In-28H1 (anti-FAP), 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 . Tracer uptake in joints correlated with arthritis score. Treatment decreased joint uptake of tracers from 23 ± 15, 8 ± 4, and 2 ± 1 percentage injected dose per gram (%ID/g) to 11 ± 11 (P , 0.001), 4 ± 4 (P , 0.001), and 1 ± 0.2 %ID/g (P , 0.01) for 111 In-28H1, 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 , respectively. Arthritis-to-blood ratios (in mice with arthritis score 2 per joint) were higher for 111 In-28H1 (5.5 ± 1; excluding values . 25), 111 In-anti-F4/80-A3-1 (10.4 ± 4), and 111 In-RGD 2 (7.2 ± 1) than for control 111 In-DP47GS (0.7 ± 0.5; P 5 0.002), 111 In-rat IgG2b (0.5 ± 0.2; P 5 0.002), or coinjection of excess RGD 2 (3.5), indicating specific uptake of all tracers in arthritic joints. Conclusion: 111 In-28H1, 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 can be used to specifically monitor the response to therapy in experimental arthritis at the molecular level. Further studies, however, still need to be performed.

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Section: Discussionmentioning

confidence: 99%

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

et al. 2015

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“…The in vivo liver targeting specificity of NbV4 in naive mice was previously demonstrated by performing SPECT and organ dissection analyses in Vsig4-deficient mice [18].…”

Section: Pinhole Spect/μct Analysis and [ 99m Tc]nb Accumulationmentioning

confidence: 96%

“…The lead compounds (NbC4 clone 22, NbV4 clone 119) were selected based on a combination of factors including high affinity binding as determined by surface plasmon resonance (0.3 and 0.9 nM, respectively), thermostability (Tm 9 60°C), high production yield and stability, and specificity for the target antigen in imaging experiments. For microscopy, NbC4 was subcloned into the pMECS vector to insert a hemagglutinin (HA) tag in between the Nb and the His tag [18]. Alternatively, Nbs were fluorescently labelled with the AlexaFluor® 647 protein labelling Kit (Invitrogen) or Nbs were radioactively labelled with Tc-99m through tricarbonyl chemistry.…”

Section: Anti-clec4f and Anti-vsig4 Nanobody Generationmentioning

confidence: 99%

“…Nbs were generated against recombinant mouse Clec4F (C4) and Vsig4 (V4) (both from R&D systems) as previously described [13,16,18]. Briefly, a phage-displayed Nb library with an estimated 7.3 × 10 7 clones was generated by PCR amplification and cloning of the variable domains of the heavy chain-only antibody from peripheral blood lymphocytes that were isolated from an alpaca (Vicugna pacos) immunized with both recombinant proteins [19].…”

Section: Anti-clec4f and Anti-vsig4 Nanobody Generationmentioning

confidence: 99%

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Molecular Imaging with Kupffer Cell-Targeting Nanobodies for Diagnosis and Prognosis in Mouse Models of Liver Pathogenesis

et al. 2016

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“…A CRIg‐specific radiolabeled Nb ( 99m Tc‐NbV4m119) was developed by Zheng et al. and evaluated for the in vivo biodistribution and detection of arthritic lesions in a mouse model of RA . 99m Tc‐V4m119 was found to accumulate in CRIg‐positive macrophages in the liver and inflamed joint lesions with good correlation with the severity of the symptoms (Figure B).…”

Section: Targeting Surface Markers On Immune Cellsmentioning

confidence: 99%

Antibody‐Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases

Lee

Cai

2018

ChemBioChem

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Chronic inflammatory diseases are often progressive, resulting not only in physical damage to patients but also social and economic burdens, making early diagnosis of them critical. Nuclear medicine techniques can enhance the detection of inflammation by providing functional as well as anatomical information when combined with other modalities such as magnetic resonance imaging, computed tomography or ultrasonography. Although small molecules and peptides were mainly used for the treatment and imaging of chronic inflammatory diseases in the past, antibodies and their fragments have also been emerging for chronic inflammatory diseases as they show high specificity to their targets and can have various biological half‐lives depending on how they are engineered. In addition, imaging with antibodies or their fragments can visualize the in vivo biodistribution of the probes or help monitor therapeutic responses, thereby providing physicians with a greater understanding of drug behavior in vivo and another means of monitoring their patients. In this review, we introduce various targets and radiolabeled antibody‐based probes for the molecular imaging of chronic inflammatory diseases in preclinical and clinical studies. Targets can be classified into three different categories: 1) cell‐adhesion molecules, 2) surface markers on immune cells, and 3) cytokines or enzymes. The limitations and future directions of using radiolabeled antibodies for imaging inflammatory diseases are also discussed.

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

Cited by 51 publications

References 33 publications

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

Molecular Imaging with Kupffer Cell-Targeting Nanobodies for Diagnosis and Prognosis in Mouse Models of Liver Pathogenesis

Antibody‐Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases

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

Cited by 51 publications

References 33 publications

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3

Molecular Imaging with Kupffer Cell-Targeting Nanobodies for Diagnosis and Prognosis in Mouse Models of Liver Pathogenesis

Antibody‐Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases

Contact Info

Product

Resources

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Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃