(64)Cu-DOTA-trastuzumab PET Imaging and HER2 Specificity of Brain Metastases in HER2-positive Breast Cancer Patients

Overview

Journal EJNMMI Res

Date 2015 Apr 9

PMID 25853014

Citations 43

Authors

Hiroaki Kurihara

Akinobu Hamada

Masayuki Yoshida

Schuichi Shimma

Jun Hashimoto

Kan Yonemori

Hitomi Tani

Yasuji Miyakita

Yousuke Kanayama

Yasuhiro Wada

Makoto Kodaira

Mayu Yunokawa

Harukaze Yamamoto

Chikako Shimizu

Kazuhiro Takahashi

Yasuyoshi Watanabe

Yasuhiro Fujiwara

Kenji Tamura

Affiliations

Soon will be listed here.

Abstract

Background: The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab.

Methods: PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab.

Results: Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS.

Conclusions: Cu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer.

Trial Registration: UMIN000004170.

Citing Articles

Preclinical evaluation of Cu-labeled cetuximab in immuno-PET for detecting sentinel lymph node metastasis in epidermal growth factor receptor-positive breast cancer.

Usui T, Miyake T, Watabe T, Kato H, Yoshii Y, Naka S Breast Cancer Res. 2025; 27(1):33.

PMID: 40055744 PMC: 11889786. DOI: 10.1186/s13058-025-01972-4.

The current landscape and prospects of antibody-drug conjugates for lung cancer brain metastases: a narrative review.

Zhou H, Zeng Y, Hida T, Hsu R, Huang Y, Dong X Transl Lung Cancer Res. 2025; 13(12):3778-3794.

PMID: 39830739 PMC: 11736593. DOI: 10.21037/tlcr-24-964.

Novel Molecular Classification of Breast Cancer with PET Imaging.

Toan N Medicina (Kaunas). 2025; 60(12.

PMID: 39768978 PMC: 11678748. DOI: 10.3390/medicina60122099.

[Cu]Cu-NOTA-Trastuzumab and [Zr]Zr-DFO-Trastuzumab in Xenografts with Varied HER2 Expression.

Simo C, Shmuel S, Vanover A, Pereira P Mol Pharm. 2024; 21(12):6311-6322.

PMID: 39471823 PMC: 11611601. DOI: 10.1021/acs.molpharmaceut.4c00777.

Advances and challenges in immunoPET methodology.

Mohr P, van Sluis J, Lub-de Hooge M, Lammertsma A, Brouwers A, Tsoumpas C Front Nucl Med. 2024; 4:1360710.

PMID: 39355220 PMC: 11440922. DOI: 10.3389/fnume.2024.1360710.

References

Lebeau A, Turzynski A, Braun S, Behrhof W, Fleige B, Schmitt W . Reliability of human epidermal growth factor receptor 2 immunohistochemistry in breast core needle biopsies. J Clin Oncol. 2010; 28(20):3264-70. DOI: 10.1200/JCO.2009.25.9366. View

Ono M, Ando M, Yunokawa M, Nakano E, Yonemori K, Matsumoto K . Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer. Int J Clin Oncol. 2009; 14(1):48-52. DOI: 10.1007/s10147-008-0797-8. View

Lampson L . Monoclonal antibodies in neuro-oncology: Getting past the blood-brain barrier. MAbs. 2010; 3(2):153-60. PMC: 3092616. DOI: 10.4161/mabs.3.2.14239. View

Houssami N, Macaskill P, Balleine R, Bilous M, Pegram M . HER2 discordance between primary breast cancer and its paired metastasis: tumor biology or test artefact? Insights through meta-analysis. Breast Cancer Res Treat. 2011; 129(3):659-74. DOI: 10.1007/s10549-011-1632-x. View

Jain R . Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Res. 1990; 50(3 Suppl):814s-819s. View

Mortimer J, Bading J, Colcher D, Conti P, Frankel P, Carroll M . Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. J Nucl Med. 2013; 55(1):23-9. PMC: 4084518. DOI: 10.2967/jnumed.113.122630. View

Miller K, Weathers T, Haney L, Timmerman R, Dickler M, Shen J . Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol. 2003; 14(7):1072-7. DOI: 10.1093/annonc/mdg300. View

Romond E, Perez E, Bryant J, Suman V, Geyer Jr C, Davidson N . Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1673-84. DOI: 10.1056/NEJMoa052122. View

Eichler A, Loeffler J . Multidisciplinary management of brain metastases. Oncologist. 2007; 12(7):884-98. DOI: 10.1634/theoncologist.12-7-884. View

10.

Leyland-Jones B . Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol. 2009; 27(31):5278-86. DOI: 10.1200/JCO.2008.19.8481. View

11.

Xiao C, Gong Y, Han E, Gonzalez-Angulo A, Sneige N . Stability of HER2-positive status in breast carcinoma: a comparison between primary and paired metastatic tumors with regard to the possible impact of intervening trastuzumab treatment. Ann Oncol. 2011; 22(7):1547-1553. DOI: 10.1093/annonc/mdq623. View

12.

Yonemori K, Tsuta K, Ono M, Shimizu C, Hirakawa A, Hasegawa T . Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer. 2009; 116(2):302-8. DOI: 10.1002/cncr.24735. View

13.

Tamura K, Kurihara H, Yonemori K, Tsuda H, Suzuki J, Kono Y . 64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013; 54(11):1869-75. DOI: 10.2967/jnumed.112.118612. View

14.

Buzdar A, Ibrahim N, Francis D, Booser D, Thomas E, Theriault R . Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005; 23(16):3676-85. DOI: 10.1200/JCO.2005.07.032. View

15.

Robinson M, Doss M, Shaller C, Narayanan D, Marks J, Adler L . Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody. Cancer Res. 2005; 65(4):1471-8. DOI: 10.1158/0008-5472.CAN-04-2008. View

16.

Fujimori K, Covell D, Fletcher J, Weinstein J . A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J Nucl Med. 1990; 31(7):1191-8. View

17.

Mehta A, Brufsky A, Sampson J . Therapeutic approaches for HER2-positive brain metastases: circumventing the blood-brain barrier. Cancer Treat Rev. 2012; 39(3):261-9. PMC: 4432469. DOI: 10.1016/j.ctrv.2012.05.006. View

18.

Muro H, Shirasawa H, Maeda M, Nakamura S . Fc receptors of liver sinusoidal endothelium in normal rats and humans. A histologic study with soluble immune complexes. Gastroenterology. 1987; 93(5):1078-85. DOI: 10.1016/0016-5085(87)90572-5. View

19.

Dijkers E, Munnink T, Kosterink J, Brouwers A, Jager P, de Jong J . Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010; 87(5):586-92. DOI: 10.1038/clpt.2010.12. View

20.

Tripathy D, Slamon D, Cobleigh M, Arnold A, Saleh M, Mortimer J . Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol. 2004; 22(6):1063-70. DOI: 10.1200/JCO.2004.06.557. View