Imaging of HER2 with [                         89                         Zr]pertuzumab in response to T-DM1 therapy

Adriana V.F. Massicano; Supum Lee; Bryant K. Crenshaw; Tolulope A. Aweda; Retta El Sayed; Ian Super; Ron Bose; Bernadette V. Marquez-Nostra; Suzanne E. Lapi

doi:10.1089/cbr.2018.2654

Imaging of HER2 with [ ⁸⁹ Zr]pertuzumab in response to T-DM1 therapy

Adriana V.F. Massicano, Supum Lee, Bryant K. Crenshaw, Tolulope A. Aweda, Retta El Sayed, Ian Super, Ron Bose, Bernadette V. Marquez-Nostra, Suzanne E. Lapi

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [ ⁸⁹ Zr]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with ⁸⁹ Zr. Mice bearing BT-474 tumors were imaged with [ ⁸⁹ Zr]pertuzumab and [ ¹⁸ F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with ⁸⁹ Zr with a specific activity of 0.740 MBq/μg. Overall [ ¹⁸ F]FDG images showed poor delineation of tumors. Using [ ¹⁸ F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm ³ before treatment to 89.87 ± 66.55 mm ³ after treatment. In contrast, [ ⁸⁹ Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm ³ before treatment to 78.4 ± 40.43 mm ³ after treatment). Conclusion: [ ⁸⁹ Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

Original language	English
Pages (from-to)	209-217
Number of pages	9
Journal	Cancer Biotherapy and Radiopharmaceuticals
Volume	34
Issue number	4
DOIs	https://doi.org/10.1089/cbr.2018.2654
State	Published - May 2019

Keywords

HER2-positive breast cancer
T-DM1 therapy
[ Zr]pertuzumab
molecular imaging
radiolabeled monoclonal antibody

Access to Document

10.1089/cbr.2018.2654

Cite this

Massicano, A. V. F., Lee, S., Crenshaw, B. K., Aweda, T. A., El Sayed, R., Super, I., Bose, R., Marquez-Nostra, B. V., & Lapi, S. E. (2019). Imaging of HER2 with [ ⁸⁹ Zr]pertuzumab in response to T-DM1 therapy Cancer Biotherapy and Radiopharmaceuticals, 34(4), 209-217. https://doi.org/10.1089/cbr.2018.2654

@article{7eee9d17d16e4042b7d3cfbbd66c29ec,

title = " Imaging of HER2 with [ 89 Zr]pertuzumab in response to T-DM1 therapy ",

abstract = " Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [ 89 Zr]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with 89 Zr. Mice bearing BT-474 tumors were imaged with [ 89 Zr]pertuzumab and [ 18 F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with 89 Zr with a specific activity of 0.740 MBq/μg. Overall [ 18 F]FDG images showed poor delineation of tumors. Using [ 18 F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm 3 before treatment to 89.87 ± 66.55 mm 3 after treatment. In contrast, [ 89 Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm 3 before treatment to 78.4 ± 40.43 mm 3 after treatment). Conclusion: [ 89 Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.",

keywords = "HER2-positive breast cancer, T-DM1 therapy, [ Zr]pertuzumab, molecular imaging, radiolabeled monoclonal antibody",

author = "Massicano, {Adriana V.F.} and Supum Lee and Crenshaw, {Bryant K.} and Aweda, {Tolulope A.} and {El Sayed}, Retta and Ian Super and Ron Bose and Marquez-Nostra, {Bernadette V.} and Lapi, {Suzanne E.}",

note = "Funding Information: This study was supported by UAB Department of Radiology. The authors would like to thank the members of the Lapi lab, the UAB Cyclotron Facility for production of 89Zr and Emily Brown for additional experimental assistance. The UAB small animal imaging facility is supported through the UAB Comprehensive Cancer Center P30CA013148. Publisher Copyright: {\textcopyright} 2019 Mary Ann Liebert, Inc., publishers.",

year = "2019",

month = may,

doi = "10.1089/cbr.2018.2654",

language = "English",

volume = "34",

pages = "209--217",

journal = "Cancer Biotherapy and Radiopharmaceuticals",

issn = "1084-9785",

number = "4",

}

Massicano, AVF, Lee, S, Crenshaw, BK, Aweda, TA, El Sayed, R, Super, I, Bose, R, Marquez-Nostra, BV & Lapi, SE 2019, ' Imaging of HER2 with [ ⁸⁹ Zr]pertuzumab in response to T-DM1 therapy ', Cancer Biotherapy and Radiopharmaceuticals, vol. 34, no. 4, pp. 209-217. https://doi.org/10.1089/cbr.2018.2654

Imaging of HER2 with [ ⁸⁹ Zr]pertuzumab in response to T-DM1 therapy . / Massicano, Adriana V.F.; Lee, Supum; Crenshaw, Bryant K. et al.
In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 34, No. 4, 05.2019, p. 209-217.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Imaging of HER2 with [ 89 Zr]pertuzumab in response to T-DM1 therapy

AU - Massicano, Adriana V.F.

AU - Lee, Supum

AU - Crenshaw, Bryant K.

AU - Aweda, Tolulope A.

AU - El Sayed, Retta

AU - Super, Ian

AU - Bose, Ron

AU - Marquez-Nostra, Bernadette V.

AU - Lapi, Suzanne E.

N1 - Funding Information: This study was supported by UAB Department of Radiology. The authors would like to thank the members of the Lapi lab, the UAB Cyclotron Facility for production of 89Zr and Emily Brown for additional experimental assistance. The UAB small animal imaging facility is supported through the UAB Comprehensive Cancer Center P30CA013148. Publisher Copyright: © 2019 Mary Ann Liebert, Inc., publishers.

PY - 2019/5

Y1 - 2019/5

N2 - Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [ 89 Zr]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with 89 Zr. Mice bearing BT-474 tumors were imaged with [ 89 Zr]pertuzumab and [ 18 F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with 89 Zr with a specific activity of 0.740 MBq/μg. Overall [ 18 F]FDG images showed poor delineation of tumors. Using [ 18 F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm 3 before treatment to 89.87 ± 66.55 mm 3 after treatment. In contrast, [ 89 Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm 3 before treatment to 78.4 ± 40.43 mm 3 after treatment). Conclusion: [ 89 Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

AB - Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [ 89 Zr]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with 89 Zr. Mice bearing BT-474 tumors were imaged with [ 89 Zr]pertuzumab and [ 18 F]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with 89 Zr with a specific activity of 0.740 MBq/μg. Overall [ 18 F]FDG images showed poor delineation of tumors. Using [ 18 F]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 ± 20.7 mm 3 before treatment to 89.87 ± 66.55 mm 3 after treatment. In contrast, [ 89 Zr]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 ± 40.91 mm 3 before treatment to 78.4 ± 40.43 mm 3 after treatment). Conclusion: [ 89 Zr]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

KW - HER2-positive breast cancer

KW - T-DM1 therapy

KW - [ Zr]pertuzumab

KW - molecular imaging

KW - radiolabeled monoclonal antibody

UR - http://www.scopus.com/inward/record.url?scp=85065606402&partnerID=8YFLogxK

U2 - 10.1089/cbr.2018.2654

DO - 10.1089/cbr.2018.2654

M3 - Article

C2 - 30676778

AN - SCOPUS:85065606402

SN - 1084-9785

VL - 34

SP - 209

EP - 217

JO - Cancer Biotherapy and Radiopharmaceuticals

JF - Cancer Biotherapy and Radiopharmaceuticals

IS - 4

ER -

Imaging of HER2 with [ ⁸⁹ Zr]pertuzumab in response to T-DM1 therapy

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this