Preclinical Evaluation of a Radioiodinated Fully Human Antibody for In Vivo Imaging of Vascular Adhesion Protein-1–Positive Vasculature in Inflammation

Autio, Anu; Vainio, Paula; Suilamo, Sami; Mali, Antti; Vainio, Jani; Saanijoki, Tiina; Noponen, Tommi; Ahtinen, Helena; Luoto, Pauliina; Teräs, Mika; Jalkanen, Sirpa; Roivainen, Anne

doi:10.2967/jnumed.113.120295

Cited by 20 publications

(22 citation statements)

References 17 publications

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“…In vitro and in vivo experiments show that genetically engineered chimeric monoclonal mouse-human antibodies can block sites used by AOC3 to promote leukocyte transmigration in humans without leading to side effects caused by immunogenecity or activation of effector functions (80). BTT-1023 (81), a fully human monoclonal antibody that specifically binds to AOC3, has been developed and has shown promising efficacy and safety in early clinical studies in rheumatoid arthritis and psoriasis patients, and in a range of preclinical models of inflammatory diseases, including chronic obstructive pulmonary disease (COPD), certain neurological conditions, and certain niche liver inflammatory fibrotic diseases. Currently, it is undergoing phase 2 clinical trials.…”

Section: Amine Oxidase (Copper-containing) Familymentioning

confidence: 99%

Human copper-dependent amine oxidases

Finney

Moon

Ronnebaum

et al. 2014

Archives of Biochemistry and Biophysics

112

121

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Copper amine oxidases (CAOs) are a class of enzymes that contain Cu2+ and a tyrosine-derived quinone cofactor, catalyze the conversion of a primary amine functional group to an aldehyde, and generate hydrogen peroxide and ammonia as byproducts. These enzymes can be classified into two non-homologous families: 2,4,5-trihydroxyphenylalanine quinone (TPQ)-dependent CAOs and the lysine tyrosylquinone (LTQ)-dependent lysyl oxidase (LOX) family of proteins. In this review, we will focus on recent developments in the field of research concerning human CAOs and the LOX family of proteins. The aberrant expression of these enzymes is linked to inflammation, fibrosis, tumor metastasis/invasion and other diseases. Consequently, there is a critical need to understand the functions of these proteins at the molecular level, so that strategies targeting these enzymes can be developed to combat human diseases.

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Section: Amine Oxidase (Copper-containing) Familymentioning

confidence: 99%

Human copper-dependent amine oxidases

Finney

Moon

Ronnebaum

et al. 2014

Archives of Biochemistry and Biophysics

112

121

View full text Add to dashboard Cite

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“…It was shown that serum levels of sVAP1 are markedly elevated in patients with chronic inflammatory liver diseases [120]. Blockade of VAP1 inhibits inflammatory responses by attenuating leukocyte recruitment and oxidative stress [120, 121]. BTT-1023, a human monoclonal antibody against VAP1, will be assessed in the clinical study in patients with primary sclerosing cholangitis.…”

Section: Developments In Targeted Therapy Related To Liver Fibrosismentioning

confidence: 99%

“…This autoimmune liver disease is characterized by the progressive destruction of the hepatic bile ducts, which in turn leads to liver fibrosis and cholestasis [122]. Preclinical studies showed efficient binding of the antibody with VAP1 in the inflamed sites in vivo , as assessed by PET scans [121]. …”

Section: Developments In Targeted Therapy Related To Liver Fibrosismentioning

confidence: 99%

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

Bansal

Nagórniewicz

Prakash

2016

Mediators of Inflammation

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Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.

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“…BTT-1023 is an anti-VAP-1 mAb for the treatment of inflammatory diseases. In a recent study, radioiodinated BTT-1023 was adopted for inflammation imaging in a rabbit model of arthritis [238]. Pharmacokinetics of 124 I-BTT-1023 was elucidated by PET/CT up to 72 h after injection.…”

Section: Pet or Spect Imaging Of Vascular Targets In Inflammationmentioning

confidence: 99%

“…Pharmacokinetics of 124 I-BTT-1023 was elucidated by PET/CT up to 72 h after injection. Rabbits with chemically induced synovitis were imaged with 123 I-BTT-1023 SPECT/CT [238]. Radioiodinated BTT-1023 cleared rapidly from blood circulation and distributed to liver and thyroid.…”

Section: Pet or Spect Imaging Of Vascular Targets In Inflammationmentioning

confidence: 99%

New radiotracers for imaging of vascular targets in angiogenesis-related diseases

Hong

Chen

Zhang

et al. 2014

Advanced Drug Delivery Reviews

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Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients.

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Preclinical Evaluation of a Radioiodinated Fully Human Antibody for In Vivo Imaging of Vascular Adhesion Protein-1–Positive Vasculature in Inflammation

Cited by 20 publications

References 17 publications

Human copper-dependent amine oxidases

Human copper-dependent amine oxidases

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

New radiotracers for imaging of vascular targets in angiogenesis-related diseases

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