HER2 Expression Detection in Breast Cancer Using 99mTc-NM-02

Summary

A 99mTc-labeled anti-HER2-sdAb (99mTc-NM-02) will be developed for SPECT/CT assessment of HER2 expression in breast cancer patients. Its safety, radiation dosimetry and biodistribution, and the relationship between tumor uptake and HER2 immunohistochemistry results will be investigated.

Timeline

Start

2019-07-29

Primary completion

2021-12-31

Completion

2022-03-30

Publications

• Background Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016 Jul;22(7):723-6. doi: 10.1038/nm.4120. Epub 2016 Jun 6.
• Background Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005 Oct 20;353(16):1652-4. doi: 10.1056/NEJMp058197. No abstract available.
• Background Arteaga CL, Sliwkowski MX, Osborne CK, Perez EA, Puglisi F, Gianni L. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol. 2011 Nov 29;9(1):16-32. doi: 10.1038/nrclinonc.2011.177.
• Background Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortes J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. doi: 10.1056/NEJMoa1413513.
• Background Gingras I, Gebhart G, de Azambuja E, Piccart-Gebhart M. HER2-positive breast cancer is lost in translation: time for patient-centered research. Nat Rev Clin Oncol. 2017 Nov;14(11):669-681. doi: 10.1038/nrclinonc.2017.96. Epub 2017 Aug 1.
• Background Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017 Jun 17;389(10087):2415-2429. doi: 10.1016/S0140-6736(16)32417-5. Epub 2016 Dec 7.
• Background Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol. 2012 Feb 20;30(6):593-9. doi: 10.1200/JCO.2010.33.8889. Epub 2011 Nov 28.
• Background Baum RP, Prasad V, Muller D, Schuchardt C, Orlova A, Wennborg A, Tolmachev V, Feldwisch J. Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. J Nucl Med. 2010 Jun;51(6):892-7. doi: 10.2967/jnumed.109.073239. Epub 2010 May 19.
• Background D'Huyvetter M, Vincke C, Xavier C, Aerts A, Impens N, Baatout S, De Raeve H, Muyldermans S, Caveliers V, Devoogdt N, Lahoutte T. Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody. Theranostics. 2014 Apr 25;4(7):708-20. doi: 10.7150/thno.8156. eCollection 2014.
• Background Pruszynski M, D'Huyvetter M, Bruchertseifer F, Morgenstern A, Lahoutte T. Evaluation of an Anti-HER2 Nanobody Labeled with 225Ac for Targeted alpha-Particle Therapy of Cancer. Mol Pharm. 2018 Apr 2;15(4):1457-1466. doi: 10.1021/acs.molpharmaceut.7b00985. Epub 2018 Mar 7.
• Background Puttemans J, Dekempeneer Y, Eersels JL, Hanssens H, Debie P, Keyaerts M, Windhorst AD, van der Aa F, Lecocq Q, Breckpot K, Morgenstern A, Bruchertseifer F, Lahoutte T, Devoogdt N, D'Huyvetter M. Preclinical Targeted alpha- and beta--Radionuclide Therapy in HER2-Positive Brain Metastasis Using Camelid Single-Domain Antibodies. Cancers (Basel). 2020 Apr 21;12(4):1017. doi: 10.3390/cancers12041017.
• Zhao L, Liu C, Xing Y, He J, O'Doherty J, Huang W, Zhao J. Development of a 99mTc-Labeled Single-Domain Antibody for SPECT/CT Assessment of HER2 Expression in Breast Cancer. Mol Pharm. 2021 Sep 6;18(9):3616-3622. doi: 10.1021/acs.molpharmaceut.1c00569. Epub 2021 Jul 30.

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