Nanoparticles containing magnetic materials, such as magnetite (Fe3O4), are particularly useful for imaging and separation techniques. As these nanoparticles are generally considered to be biologically and chemically inert, they are typically coated with metal catalysts, antibodies or enzymes to increase their functionality as separation agents. Here, we report that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools. Based on this finding, we have developed a novel immunoassay in which antibody-modified magnetite nanoparticles provide three functions: capture, separation and detection. The stability, ease of production and versatility of these nanoparticles makes them a powerful tool for a wide range of potential applications in medicine, biotechnology and environmental chemistry.

Intrinsic peroxidase-like activity of ferromagnetic nanoparticles

The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

Long-Circulating and Target-Specific Nanoparticles: Theory to Practice

The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

/pdf/integrins-in-cancer-biological-implications-and-therapeutic-2ejzg8fop4.pdf

Integrins in cancer: biological implications and therapeutic opportunities

Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Multimodal anti-PSMA ligands for intra-operative tumor detection and targeted photodynamic therapy of PSMA-expressing tumors

Pretargeted immunoPET for imaging human colonic cancer in a mouse model

106 Characterization of human squamous cell head and neck carcinoma xenografts using 18F-FLT and 18F-MISO autoradiography and immunohistochemistry

Background Rheumatoid arthritis (RA) synovial tissue has been demonstrated to express high levels of fibroblast activation protein (FAP) using anti-FAP-antibody 28H1. In addition, RA patients show elevated levels of IL-22 and IL-22-producing T helper cells that correlate to erosive disease, suggesting a role for this cytokine in the pathogenesis of RA. Objectives The purpose of this study was to determine the feasibility of 111 In-28H1 SPECT/CT imaging of FAP-expressing synovium to monitor the therapeutic potential of neutralizing IL-22 during experimental arthritis. Methods Collagen-induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated 3 times per week with anti-IL-22 antibodies (8 mg/kg), while the control group received rat IgG1 isotype control antibodies. To monitor the therapeutic effect after 2 weeks of treatment, SPECT/CT images were acquired 24 h after injection of 111 In-labeled DTPA-conjugated anti-FAP antibody, 28H1. After image acquisition, mice were euthanized and dissected. Imaging results were compared with the macroscopic arthritis scores and radiographic bone damage scores acquired by X-ray. Results Blocking IL-22 during CIA was a potent approach to prevent arthritis development, reaching a disease incidence of only 50%, versus 100% in the control group. SPECT/CT imaging using indium-labeled anti-FAP antibodies showed that joint uptake of the tracer was reduced highly significant (p=0.002) in anti-IL-22-treated mice (4.3 ± 3.4%ID/g) compared to the isotype control group (12.7 ± 3.7%ID/g) (See figure). This was confirmed by the corresponding macroscopic arthritis scores and radiographic bone damage scores that were significantly (p=0.047 and p=0.017 respectively) lower in the anti-IL-22-treated group. Besides its sensitivity, the in vivo FAP-based SPECT/CT had the great advantage to visualize sites of inflammation that were overlooked during clinical scoring, like in knee, hip, elbow and shoulder (See figure). Conclusions These findings demonstrate that IL-22 plays an important role in the development of experimental arthritis, and targeting this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging of the inflamed synovium using the labeled anti-FAP antibody 111 In-DTPA-28H1 can be used to specifically monitor response to therapy in an objective and quantitative way, and is potentially more sensitive in disease monitoring compared to the standard method of clinical arthritis scoring by macroscopic inspection. Disclosure of Interest D. Roeleveld: None declared, T. van der Geest: None declared, T. Nayak Employee of: Roche, C. Klein Employee of: Roche, B. Walgreen: None declared, M. Helsen: None declared, M. Hegen Employee of: Pfizer, P. Laverman: None declared, O. Boerman: None declared, M. Koenders: None declared

https://ard.bmj.com/content/annrheumdis/76/Suppl_1/A9.2.full.pdf

OP0075 Sensitive Spect/CT Imaging of Synovial Fap Expression after Anti-IL-22 Treatment in Experimental Arthritis

Periodontitis is one of the most common inflammatory diseases, which can lead to early tooth loss. The conventional treatment of periodontitis is to arrest the disease progression. Most reconstructive procedures involve application of bone substitutes, barrier membranes or a combination of both into the bony defects. Calcium phosphate cements (CPCs) are the predominant type of bone substitute material used for reasons of injectability and hence perfect filling potential for bone defects. Recently, injectable apatitic CPCs demonstrated to be more rapidly degradable when combined with poly (lactic-co-glycolic) acid (PLGA) microspheres. Further, PLGA microspheres can be used as a delivery vehicle for growth factors. In this study, the performance of injectable CPCs as a bone substitute material for alveolar bone defects created in Beagle dogs was evaluated. Four CPC-formulations were generated by incorporating hollow or dense PLGA microspheres, either or not loaded with the growth factors (platelet derived growth factor (PDGF) and insulin-like growth factor (IGF). Implantation period was 8 weeks. Bone formation was based on histological and histomorphometrical evaluation. The results demonstrated that filling alveolar bone defects with CPC-dense PLGA revealed significant more bone formation compared to CPC-hollow PLGA either or not loaded with IGF and PDGF. In summary, we conclude that injectable CPC-dense PLGA composites proved to be the most suitable material for a potential use as off the shelf material due to its good biocompatibility, enhanced degradability and subsequent bone formation.

Otto C. Boerman

Papers

Multimodal anti-PSMA ligands for intra-operative tumor detection and targeted photodynamic therapy of PSMA-expressing tumors

Pretargeted immunoPET for imaging human colonic cancer in a mouse model

106 Characterization of human squamous cell head and neck carcinoma xenografts using 18F-FLT and 18F-MISO autoradiography and immunohistochemistry

OP0075 Sensitive Spect/CT Imaging of Synovial Fap Expression after Anti-IL-22 Treatment in Experimental Arthritis

Bone Regenerative Properties of Injectable Calcium Phosphate/PLGA Cement in an Alveolar Bone Defect