Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer

Henry, Kelly E.; Ulaner, Gary A.; Lewis, Jason S.

doi:10.1016/j.cpet.2018.02.010

Cited by 24 publications

(15 citation statements)

References 61 publications

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“…Therefore, determination of HER2 expression level is strongly recommended in breast and gastroesophageal cancers (Wolff et al 2013;Van Cutsem et al 2015). Development of probes for imaging of HER2 was pursued for many years, and a number of excellent reviews have been recently published on this topic (Gebhart et al 2016;Henry et al 2018;Massicano et al 2018). Therefore, we will limit ourselves here to comparison of preclinical data for representative examples of imaging probes for PET.…”

Section: Her2mentioning

confidence: 99%

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

Garousi

Orlova

Frejd

et al. 2020

EJNMMI radiopharm. chem.

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The use of radiolabelled antibodies was proposed in 1970s for staging of malignant tumours. Intensive research established chemistry for radiolabelling of proteins and understanding of factors determining biodistribution and targeting properties. The use of radioimmunodetection for staging of cancer was not established as common practice due to approval and widespread use of [ 18 F]-FDG, which provided a more general diagnostic use than antibodies or their fragments. Expanded application of antibody-based therapeutics renewed the interest in radiolabelled antibodies. RadioimmunoPET emerged as a powerful tool for evaluation of pharmacokinetics of and target engagement by biotherapeutics. In addition to monoclonal antibodies, new radiolabelled engineered proteins have recently appeared, offering highcontrast imaging of expression of therapeutic molecular targets in tumours shortly after injection. This creates preconditions for noninvasive determination of a target expression level and stratification of patients for targeted therapies. Radiolabelled proteins hold great promise to play an important role in development and implementation of personalised targeted treatment of malignant tumours. This article provides an overview of biodistribution and tumour-seeking features of major classes of targeting proteins currently utilized for molecular imaging. Such information might be useful for researchers entering the field of the protein-based radionuclide molecular imaging.

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Section: Her2mentioning

confidence: 99%

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

Garousi

Orlova

Frejd

et al. 2020

EJNMMI radiopharm. chem.

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“…HER3 was discovered later and the level of HER3 overexpression in cancer is relatively low compared with HER1 and HER2 [ 29 , 30 ]. HER3 overexpression has for example been associated with breast, ovarian, gastric, and prostate cancer [ 31 , 32 , 33 , 34 , 35 ] and linked to poor survival [ 33 , 36 ]. It has been shown that HER3 expression can be upregulated in response to HER1 or HER2 targeted therapies to compensate for proliferative signaling loss by activation of the PI3K/Akt pathway [ 37 , 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

Rinne

Orlova

Tolmachev

2021

IJMS

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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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“… 17 Hence, these techniques might provide the HER2 expression assessment in primary and secondary lesions, in particular when it is not achievable by biopsy. 18 , 19 Related to this, new advances in Nanomedicine have led to the development of nanoparticles (NPs) for the simultaneous diagnosis and treatment of human cancer (theranostic), offering the possibility to improve the efficiency and safety of conventional anticancer treatments and allowing a tailored care of patient. 20 Nanotechnologies in Nuclear Medicine are offering innovative radiolabeled probes, which are able to host various functionalities in order to improve specificity and sensitivity versus the target, with multi-labeling chance for multimodal imaging techniques.…”

Section: Introductionmentioning

confidence: 99%

99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

Rainone¹,

Palma²,

Sudati³

et al. 2021

IJN

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Introduction The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC. Methods Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99m Tc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors. Results SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls. Conclusion These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles.

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Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer

Cited by 24 publications

References 61 publications

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

99mTc-Radiolabeled Silica Nanocarriers for Targeted Detection and Treatment of HER2-Positive Breast Cancer

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