Targeted Nanobody-Based Molecular Tracers for Nuclear Imaging and Image-Guided Surgery

Debie, Pieterjan; Devoogdt, Nick; Hernot, Sophie

doi:10.3390/antib8010012

Cited by 82 publications

(93 citation statements)

References 123 publications

(164 reference statements)

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“…High antigen specificity is crucial for reducing side effects and minimizing the chance of obtaining false positives [54]. However, for molecular imaging, nanobodies have to be labelled with a diagnostic radioisotope, which can be gamma-emitting nuclides for single photon emission computed tomography (SPECT) or positron-emitting nuclides for positron emission tomography (PET) [70]. PET isotopes 68 Ga and 18 F are most appropriate for human use due to the short half-lives of 68 and 110 min, respectively.…”

Section: Nanobodies the Smaller Variant Of Antibodiesmentioning

confidence: 99%

The Therapeutic Potential of Nanobodies

2019

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Today, bio-medical efforts are entering the subcellular level, which is witnessed with the fast-developing fields of nanomedicine, nanodiagnostics and nanotherapy in conjunction with the implementation of nanoparticles for disease prevention, diagnosis, therapy and follow-up. Nanoparticles or nanocontainers offer advantages including high sensitivity, lower toxicity and improved safety-characteristics that are especially valued in the oncology field. Cancer cells develop and proliferate in complex microenvironments leading to heterogeneous diseases, often with a fatal outcome for the patient. Although antibody-based therapy is widely used in the clinical care of patients with solid tumours, its efficiency definitely needs improvement. Limitations of antibodies result mainly from their big size and poor penetration in solid tissues. Nanobodies are a novel and unique class of antigen-binding fragments, derived from naturally occurring heavy-chain-only antibodies present in the serum of camelids. Their superior properties such as small size, high stability, strong antigen-binding affinity, water solubility and natural origin make them suitable for development into next-generation biodrugs. Less than 30 years after the discovery of functional heavy-chain-only antibodies, the nanobody derivatives are already extensively used by the biotechnology research community. Moreover, a number of nanobodies are under clinical investigation for a wide spectrum of human diseases including inflammation, breast cancer, brain tumours, lung diseases and infectious diseases. Recently, caplacizumab, a bivalent nanobody, received approval from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treatment of patients with thrombotic thrombocytopenic purpura.

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Section: Nanobodies the Smaller Variant Of Antibodiesmentioning

confidence: 99%

The Therapeutic Potential of Nanobodies

2019

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“…A nanobody-based drug that targets von Willebrand factor has received approval from the US Food and Drug Administration (FDA), 84,85 and several more nanobodies are in clinical trials. 37,65,86,87 As nanobodies are derived from camelid heavy-chain-only antibodies, they can be immunogenic in humans. However, the VHH framework regions are homologous to those of human IgGs, 88,89 which may explain their low immunogenicity in clinical settings.…”

Section: Immunogenicity and Safety Profile Of Nanobodiesmentioning

confidence: 99%

Nanobodies as non-invasive imaging tools

Rashidian

Ploegh

2020

Immuno-Oncology Technology

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Antibodies and antibody fragments have found wide application for therapeutic and diagnostic purposes. Single-domain antibody fragments, also known as 'heavy-chain variable domains' or 'nanobodies', are a recent addition to the toolbox. Discovered some 30 years ago, nanobodies are the smallest antibody-derived fragments that retain antigen-binding properties. Their small size, stability, specificity, affinity and ease of manufacture make them appealing for use as imaging agents in the laboratory and the clinic. With the recent surge in immunotherapeutics and the success of cancer immunotherapy, it is important to be able to image immune responses and cancer biomarkers non-invasively to allocate resources and guide the best possible treatment of patients with cancer. This article reviews recent advances in the application of nanobodies as cancer imaging agents. While much work has been done in preclinical models, first-inhuman applications are beginning to show the value of nanobodies as imaging agents.

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“…Empirical data suggest that a reduction in the size of targeting proteins permits the ability to obtain a high imaging contrast earlier than several days after the injection [9]. Indeed, the use of a single-domain antibody (sdAb) with a molecular weight of 12-15 kDa permits the development of imaging probes with a tumor-to-blood ratio of 10-30 at 1 h after injection in murine models [10]. Mathematical modeling predicts that a further size reduction would enable an increase in tumor accumulation if the affinity of imaging probes was high enough [11,12].…”

Section: Introductionmentioning

confidence: 99%

Affibody Molecules as Targeting Vectors for PET Imaging

Tolmachev

Orlova

2020

Cancers

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Affibody molecules are small (58 amino acids) engineered scaffold proteins that can be selected to bind to a large variety of proteins with a high affinity. Their small size and high affinity make them attractive as targeting vectors for molecular imaging. High-affinity affibody binders have been selected for several cancer-associated molecular targets. Preclinical studies have shown that radiolabeled affibody molecules can provide highly specific and sensitive imaging on the day of injection; however, for a few targets, imaging on the next day further increased the imaging sensitivity. A phase I/II clinical trial showed that 68Ga-labeled affibody molecules permit an accurate and specific measurement of HER2 expression in breast cancer metastases. This paper provides an overview of the factors influencing the biodistribution and targeting properties of affibody molecules and the chemistry of their labeling using positron emitters.

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Targeted Nanobody-Based Molecular Tracers for Nuclear Imaging and Image-Guided Surgery

Cited by 82 publications

References 123 publications

The Therapeutic Potential of Nanobodies

The Therapeutic Potential of Nanobodies

Nanobodies as non-invasive imaging tools

Affibody Molecules as Targeting Vectors for PET Imaging

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