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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 30

PMID 33915894

Citations 15

Authors

Sara S Rinne

Anna Orlova

Vladimir Tolmachev

Affiliations

Soon will be listed here.

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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References

Cai W, Chen K, He L, Cao Q, Koong A, Chen X . Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur J Nucl Med Mol Imaging. 2007; 34(6):850-8. DOI: 10.1007/s00259-006-0361-6. View

Wallberg H, Orlova A . Slow internalization of anti-HER2 synthetic affibody monomer 111In-DOTA-ZHER2:342-pep2: implications for development of labeled tracers. Cancer Biother Radiopharm. 2008; 23(4):435-42. DOI: 10.1089/cbr.2008.0464. View

Divgi C, Welt S, KRIS M, Real F, Yeh S, Gralla R . Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J Natl Cancer Inst. 1991; 83(2):97-104. DOI: 10.1093/jnci/83.2.97. View

van Scheltinga A, Lub-de Hooge M, Abiraj K, Schroder C, Pot L, Bossenmaier B . ImmunoPET and biodistribution with human epidermal growth factor receptor 3 targeting antibody ⁸⁹Zr-RG7116. MAbs. 2014; 6(4):1051-8. PMC: 4171008. DOI: 10.4161/mabs.29097. View

Orlova A, Wallberg H, Stone-Elander S, Tolmachev V . On the selection of a tracer for PET imaging of HER2-expressing tumors: direct comparison of a 124I-labeled affibody molecule and trastuzumab in a murine xenograft model. J Nucl Med. 2009; 50(3):417-25. DOI: 10.2967/jnumed.108.057919. View

Maennling A, Tur M, Niebert M, Klockenbring T, Zeppernick F, Gattenlohner S . Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials. Cancers (Basel). 2019; 11(12). PMC: 6966464. DOI: 10.3390/cancers11121826. View

Garousi J, Orlova A, Frejd F, Tolmachev V . Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond. EJNMMI Radiopharm Chem. 2020; 5(1):16. PMC: 7311618. DOI: 10.1186/s41181-020-00094-w. View

Tolmachev V, Tran T, Rosik D, Sjoberg A, Abrahmsen L, Orlova A . Tumor targeting using affibody molecules: interplay of affinity, target expression level, and binding site composition. J Nucl Med. 2012; 53(6):953-60. DOI: 10.2967/jnumed.111.101527. View

Ulaner G, Hyman D, Lyashchenko S, Lewis J, Carrasquillo J . 89Zr-Trastuzumab PET/CT for Detection of Human Epidermal Growth Factor Receptor 2-Positive Metastases in Patients With Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. Clin Nucl Med. 2017; 42(12):912-917. PMC: 5708879. DOI: 10.1097/RLU.0000000000001820. View

10.

Yokota T, Milenic D, Whitlow M, Schlom J . Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992; 52(12):3402-8. View

11.

Miao Z, Ren G, Liu H, Jiang L, Cheng Z . Small-animal PET imaging of human epidermal growth factor receptor positive tumor with a 64Cu labeled affibody protein. Bioconjug Chem. 2010; 21(5):947-54. DOI: 10.1021/bc900515p. View

12.

Chung Y, Kim S, Hong J, Lee J, Lee N, Lee Y . Overexpression of HER2/HER3 and clinical feature of ovarian cancer. J Gynecol Oncol. 2019; 30(5):e75. PMC: 6658608. DOI: 10.3802/jgo.2019.30.e75. View

13.

Rinne S, Leitao C, Gentry J, Mitran B, Abouzayed A, Tolmachev V . Increase in negative charge of Ga/chelator complex reduces unspecific hepatic uptake but does not improve imaging properties of HER3-targeting affibody molecules. Sci Rep. 2019; 9(1):17710. PMC: 6881397. DOI: 10.1038/s41598-019-54149-3. View

14.

Ulaner G, Hyman D, Ross D, Corben A, Chandarlapaty S, Goldfarb S . Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT. J Nucl Med. 2016; 57(10):1523-1528. PMC: 5050126. DOI: 10.2967/jnumed.115.172031. View

15.

Akhter M, Sateesh Madhav N, Ahmad J . Epidermal growth factor receptor based active targeting: a paradigm shift towards advance tumor therapy. Artif Cells Nanomed Biotechnol. 2018; 46(sup2):1188-1198. DOI: 10.1080/21691401.2018.1481863. View

16.

Rosestedt M, Andersson K, Mitran B, Rinne S, Tolmachev V, Lofblom J . Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression. Int J Oncol. 2017; 51(6):1765-1774. DOI: 10.3892/ijo.2017.4152. View

17.

Pool M, Kol A, de Jong S, de Vries E, Lub-de Hooge M, van Scheltinga A . Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment. MAbs. 2017; 9(8):1370-1378. PMC: 5680796. DOI: 10.1080/19420862.2017.1371382. View

18.

DHuyvetter M, Vos J, Caveliers V, Vaneycken I, Heemskerk J, Duhoux F . Phase I Trial of I-GMIB-Anti-HER2-VHH1, a New Promising Candidate for HER2-Targeted Radionuclide Therapy in Breast Cancer Patients. J Nucl Med. 2020; 62(8):1097-1105. DOI: 10.2967/jnumed.120.255679. View

19.

Zhao P, Yang X, Qi S, Liu H, Jiang H, Hoppmann S . Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes. Biomed Res Int. 2013; 2013:759057. PMC: 3654646. DOI: 10.1155/2013/759057. View

20.

Ahlgren S, Orlova A, Wallberg H, Hansson M, Sandstrom M, Lewsley R . Targeting of HER2-expressing tumors using 111In-ABY-025, a second-generation affibody molecule with a fundamentally reengineered scaffold. J Nucl Med. 2010; 51(7):1131-8. DOI: 10.2967/jnumed.109.073346. View