| 1. |
- Bragina, Olga D., et al.
(författare)
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The Evolution of Targeted Radionuclide Diagnosis of HER2-Positive Breast Cancer
- 2022
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Ingår i: ACTA NATURAE. - : RUSSIAN FEDERATION AGENCY SCIENCE & INNOVATION. - 2075-8251 .- 2075-8243. ; 14:2, s. 4-15
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Forskningsöversikt (refereegranskat)abstract
- This review examines the evolution of the radionuclide diagnosis of HER2-positive breast cancer using various compounds as a targeting module in clinical practice: from full-length antibodies to a new group of small synthetic proteins called alternative scaffold proteins. This topic is of especial relevance today in view of the problems attendant to the detection of breast cancer with HER2/neu overexpression, which, in most cases, introduce errors in the treatment of patients. The results of clinical studies of radiopharmaceuticals based on affibody molecules, ADAPTs, and DARPins for SPECT and PET have demonstrated good tolerability of the compounds, their rapid excretion from the body, and the possibility to differentiate tumor sites depending on the HER2/neu status. This indicates that targeted radionuclide diagnosis holds promise and the need to continue research in this direction.
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| 2. |
- Tolmachev, Vladimir, et al.
(författare)
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Targeted nuclear medicine. Seek and destroy
- 2022
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Ingår i: Russian Chemical Reviews. - : IOP Publishing. - 0036-021X .- 1468-4837. ; 91:3
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Forskningsöversikt (refereegranskat)abstract
- The targeted delivery of radionuclides to tumours holds great promise for diagnosis and treatment of malignant neoplasms. The development of scaffold proteins has significantly simplified the design of targeting agents with desirable properties. This review comprehensively describes the key aspects of the design of radionuclide compounds, including classification of radionuclides, methodology for their attachment to targeting agents and characteristics of these agents that affect their behaviour in the body. Various targeting molecules are compared in terms of their ability to specifically find malignant foci in the body. The most recent achievements of cancer theranostics that aim at increasing the selectivity of antitumour effect are described, such as the fusion of targeting scaffold proteins with the albumin-binding domain and pretargeting. Special attention is paid to the creation of targeted radionanomaterials. Advantages and disadvantages of different strategies are analyzed and approaches for improving the delivery to tumours and for minimizing the undesirable impact on healthy organs and tissues are proposed. Particular emphasis is placed on the results of studies published in 2020 ?? 2021 that have not yet been covered by reviews.
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| 3. |
- Ahlgren, Sara, et al.
(författare)
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Radionuclide molecular imaging using affibody molecules
- 2010
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Ingår i: Current Pharmaceutical Biotechnology. - : Bentham Science Publishers Ltd.. - 1389-2010 .- 1873-4316. ; 11:6, s. 581-589
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Forskningsöversikt (refereegranskat)abstract
- The current way to increase efficacy of cancer therapy is the use of molecular recognition of aberrantly expressed gene products for selective treatment. However, only a fraction of the patients have tumors with a particular molecular target. Radionuclide imaging of molecular targets might help to stratify patient for cancer treatment. Affibody molecules are scaffold proteins, which can be selected for high affinity recognition of proteinaceous molecular targets. The capacity to re-fold under physiological conditions allows labeling of Affibody molecules in a broad range of pH and temperatures with preserved binding properties. Peptide synthesis or introduction of a unique cysteine enables site-specific labeling of Affibody molecules, resulting in uniform conjugates with well-defined pharmacological characteristics. The small size (7 kDa) of Affibody molecules provides rapid extravasation, rapid tumor penetration, and rapid clearance of unbound tracer from healthy organs and tissues. In combination with sub-nanomolar affinity, this results in high contrast in vivo imaging a few hours after injection. Excellent targeting has been demonstrated in pre-clinical studies with HER2-targeting Affibody molecules labeled with (99m)Tc and (111)In for single photon computed tomography (SPECT), and (18)F, (64)Cu, (124)I and (68)Ga for positron emission tomography (PET). Pilot clinical data confirm the high potential of Affibody molecules.
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| 4. |
- Eissler, Nina, et al.
(författare)
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Affibody PET Imaging of HER2-Expressing Cancers as a Key to Guide HER2-Targeted Therapy
- 2024
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 12:5
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Forskningsöversikt (refereegranskat)abstract
- Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15-20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody-drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody((R)) molecules, small, engineered affinity proteins with a size of similar to 6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.
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| 5. |
- Löfblom, John, et al.
(författare)
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Affibody molecules : Engineered proteins for therapeutic, diagnostic and biotechnological applications
- 2010
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 584:12, s. 2670-2680
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Forskningsöversikt (refereegranskat)abstract
- Affibody molecules are a class of engineered affinity proteins with proven potential for therapeutic, diagnostic and biotechnological applications. Affibody molecules are small (6.5 kDa) single domain proteins that can be isolated for high affinity and specificity to any given protein target. Fifteen years after its discovery, the Affibody technology is gaining use in many groups as a tool for creating molecular specificity wherever a small, engineering compatible tool is warranted. Here we summarize recent results using this technology, propose an Affibody nomenclature and give an overview of different HER2-specific Affibody molecules. Cumulative evidence suggests that the three helical scaffold domain used as basis for these molecules is highly suited to create a molecular affinity handle for vastly different applications.
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| 6. |
- Mitran, Bogdan, et al.
(författare)
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Radiolabeled GRPR Antagonists for Imaging of Disseminated Prostate Cancer : Influence of Labeling Chemistry on Targeting Properties
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:41, s. 7090-7111
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Radionuclide molecular imaging of gastrin-releasing peptide receptor (GRPR) expression promises unparalleled opportunities for visualizing subtle prostate tumors, which due to small size, adjacent benign tissue, or a challenging location would otherwise remain undetected by conventional imaging. Achieving high imaging contrast is essential for this purpose and the molecular design of any probe for molecular imaging of prostate cancer should be aimed at obtaining as high tumor-to-organ ratios as possible.OBJECTIVE: This short review summarizes the key imaging modalities currently used in prostate cancer, with a special focus on radionuclide molecular imaging. Emphasis is laid mainly on the issue of radiometals labeling chemistry and its influence on the targeting properties and biodistribution of radiolabeled GRPR antagonists for imaging of disseminated prostate cancer.METHODS: A comprehensive literature search of the PubMed/MEDLINE, and Scopus library databases was conducted to find relevant articles.RESULTS: The combination of radionuclide, chelator and required labeling chemistry was shown to have a significant influence on the stability, binding affinity, and internalization rate, off-target interaction with normal tissues and blood proteins, interaction with enzymes, activity uptake and retention in excretory organs and activity uptake in tumors of radiolabeled bombesin antagonistic analogues.CONCLUSION: Labeling chemistry had a very strong impact on the biodistribution profile of GRPR-targeting peptide based imaging probes and needs to be considered when designing a targeting probe for high contrast molecular imaging. Taking into account the complexity of in vivo interactions, it is not currently possible to accurately predict the optimal labeling approach. Therefore, a detailed characterization and optimization is essential for the rational design of imaging agents.
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| 7. |
- Molavipordanjani, Sajjad, et al.
(författare)
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Basic and practical concepts of radiopharmaceutical purification methods
- 2019
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Ingår i: Drug Discovery Today. - : Elsevier. - 1359-6446 .- 1878-5832. ; 24:1, s. 315-324
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Forskningsöversikt (refereegranskat)abstract
- The presence of radiochemical impurities in a radiopharmaceutical contributes to an unnecessary radiation burden for the patients or to an undesirable high radioactivity background, which reduces the imaging contrast or therapeutic efficacy. Therefore, if the radiolabeling process results in unsatisfactory radiochemical purity, a purification step is unavoidable. A successful purification process requires a profound knowledge about the radiopharmaceuticals of interest ranging from structural features to susceptibility to different conditions. Most radiopharmaceutical purification methods are based on solid phase extraction (SPE), high-performance liquid chromatography (HPLC), size exclusion chromatography (SEC), ion-exchange chromatography (IEC), and liquid-liquid extraction (LLE). Here, we discuss the basic and applied concepts of these purifications methods as well as their advantages and limitations.
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| 8. |
- Nilsson, Fredrik Y., et al.
(författare)
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Affibody molecules : new protein domains for molecular imaging and targeted tumor therapy
- 2007
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Ingår i: Current opinion in drug discovery & development. - 1367-6733 .- 2040-3437. ; 10:2, s. 167-175
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Forskningsöversikt (refereegranskat)abstract
- Molecular imaging shows promise as a useful tool to aid drug discovery and development and also to provide important prognostic and predictive diagnostic information affecting patient management in the clinic. However, the use of molecular imaging diagnostically is not widely adopted, in part due to the lack of suitable targeting agents. Affibody molecules are a class of small and very stable protein domains, which can be used to selectively address a wide range of protein targets. Their small size enables high contrast radionuclide imaging and they can be produced by conventional peptide synthesis methods. Their potential utility in molecular imaging is highlighted in a large number of animal studies using anti-HER2 Affibody tracers and has recently been validated in breast cancer patients with HER2-expressing metastases. The therapeutic efficacy of the Affibody molecules in this indication was demonstrated in preclinical models using a targeted radionuclide as the effector function. This review will focus on the recent use of Affibody molecules for molecular imaging and their application for radioimmunotherapy.
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| 9. |
- Rinne, Sara S., et al.
(författare)
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PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:7
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Forskningsöversikt (refereegranskat)abstract
- The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.
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| 10. |
- Tolmachev, Vladimir, et al.
(författare)
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Affibody molecules : potential for in vivo imaging of molecular targets for cancer therapy
- 2007
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Ingår i: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 7:4, s. 555-568
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Forskningsöversikt (refereegranskat)abstract
- Targeting radionuclide imaging of tumor-associated antigens may help to select patients who will benefit from a particular biological therapy. Affibody molecules are a novel class of small (approximately 7 kDa) phage display-selected affinity proteins, based on the B-domain scaffold of staphylococcal protein A. A large library (3 x 10(9) variants) has enabled selection of high-affinity (up to 22 pM) binders for a variety of tumor-associated antigens. The small size of Affibody molecules provides rapid tumor localization and fast clearance from nonspecific compartments. Preclinical studies have demonstrated the potential of Affibody molecules for specific and high-contrast radionuclide imaging of HER2 in vivo, and pilot clinical data using indium-111 and gallium-68 labeled anti-HER2 Affibody tracer have confirmed its utility for radionuclide imaging in cancer patients.
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