Affibody Molecules as Targeting Vectors for PET Imaging

Tolmachev, Vladimir; Orlova, Anna

doi:10.3390/cancers12030651

Cited by 68 publications

(71 citation statements)

References 115 publications

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“…Artificial antibody like scaffold proteins allowing to spatially positioning of a set of amino acid residues ensuring interaction with a target molecule are considered as a promising type of ligands. Among them are small sized protein A based affibodies [151]. Some of them effectively interact with EGFR, but also exhibit low endocytosis rate [152].…”

Section: The Use Of Egfr As a Delivery Systemmentioning

confidence: 99%

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Rosenkranz

Slastnikova

2020

Biochemistry Moscow

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Epidermal growth factor receptor (EGFR) is an integral surface protein mediating cellular response to a number of growth factors. Its overexpression and increased activation due to mutations is one of the most common traits of many types of cancer. Development and clinical use of the agents, which block EGFR activation, became a prime example of the personalized targeted medicine. However, despite the obvious success in this area, cancer cure remains unattainable in most cases. Because of that, as well as the result of the search for possible ways to overcome the difficulties of treatment, a huge number of new treatment methods relying on the use of EGFR overexpression and its changes to destroy cancer cells. Modern data on the structure, functioning, and intracellular transport of EGFR, its natural ligands, as well as signaling cascades triggered by the EGFR activation, peculiarities of the EGFR expression and activation in oncological disorders, as well as applied therapeutic approaches aimed at blocking EGFR signaling pathway are summarized and analyzed in this review. Approaches to the targeted delivery of various chemotherapeutic agents, radionuclides, immunotoxins, photosensitizers, as well as the prospects for gene therapy aimed at cancer cells with EGFR overexpression are reviewed in detail. It should be noted that increasing attention is being paid nowadays to the development of multifunctional systems, either carrying several different active agents, or possessing several environment-dependent transport functions. Potentials of the systems based on receptor-mediated endocytosis of EGFR and their possible advantages and limitations are discussed.

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Section: The Use Of Egfr As a Delivery Systemmentioning

confidence: 99%

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Rosenkranz

Slastnikova

2020

Biochemistry Moscow

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“…Affibody molecules binding with high affinity to several clinically relevant cancer-associated molecular targets (HER2, EGFR, HER3, IGF-1R, PDGFRβ and CAIX) have been developed [4,5]. In molecular imaging, radiolabelled affibody molecules proved to be advantageous in comparison with mAbs enabling higher sensitivity and specificity [5]. Due to their small size, affibody molecules accumulate rapidly in tumours, undergo rapid washout from non-targeted tissues, and have a short residence time in the circulation.…”

Section: Introductionmentioning

confidence: 99%

Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules

2020

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Affibody molecules are the most studied class of engineered scaffold proteins (ESPs) in radionuclide molecular imaging. Attempts to use affibody molecules directly labelled with radiometals for targeted radionuclide therapy were hampered by the high uptake and retention of radioactivity in kidneys. Several promising strategies have been implemented to circumvent this problem. Here, we investigated whether a pharmacological approach targeting different components of the reabsorption system could be used to lower the uptake of [99mTc]Tc-ZHER:2395 affibody molecule in kidneys. Pre-injection of probenecid, furosemide, mannitol or colchicine had no influence on activity uptake in kidneys compared to the control group. Mice pre-injected with maleate and fructose had 33% and 51% reduction in the kidney-associated activity, respectively, compared to the control group. Autoradiography images showed that the accumulation of activity after [99mTc]Tc-ZHER2:2395 injection was in the renal cortex and that both maleate and fructose could significantly reduce it. Results from this study demonstrate that pharmacological intervention with maleate and fructose was effective in reducing the kidney uptake of affibody molecules. A presumable mechanism is the disruption of ATP-mediated cellular uptake and endocytosis processes of affibody molecules by tubular cells.

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“…For example, the low affinity of affibodies to the target is a major issue [27]. In addition, the design of the affibody molecules would have to be modified in order to reduce off-target interactions or background radioactivity [107]. However, the development of radioactively labeled affibodies is expensive and poses some challenges in scaling-up of the production process [27].…”

Section: Affibodiesmentioning

confidence: 99%

HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging

Altunay

Morgenroth

Beheshti

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development. Results Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients. Even in therapy, the small radioactively labeled nanobodies prove to be superior to radioactively labeled monoclonal antibodies due to their higher specificity and their ability to penetrate the tumor. Conclusion While monoclonal antibodies are well established drug delivery vehicles, the current literature on molecular imaging supports the notion that antibody fragments, such as affibodies or nanobodies, might be superior in this approach.

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Affibody Molecules as Targeting Vectors for PET Imaging

Cited by 68 publications

References 115 publications

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Epidermal Growth Factor Receptor: Key to Selective Intracellular Delivery

Influence of Several Compounds and Drugs on the Renal Uptake of Radiolabeled Affibody Molecules

HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging

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