Designer ⁶⁴Cu Porphyrin-Trastuzumab Conjugates for Imaging of HER2-Positive Breast Cancer.
- 1Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, United States.
- 2Department of Radiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
- 3Oncurie, Inc., Raleigh, North Carolina 27608, United States.
Abstract
The human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-30% of breast cancer cases, plays a significant role in pathogenesis, and has been used as a diagnostic indicator and therapeutic target. Herein, a bioconjugatable porphyrin chelator is described, bearing a water-solubilizing swallowtail motif that projects above and below the plane of the macrocycle. This porphyrin, in various quantities, was reacted in stochastic fashion with the lysine side chains of the anti-HER2 antibody trastuzumab to afford a series of porphyrin-trastuzumab (PorTraz) products with conjugation ratios of 2.3, 3.5, 4.1, and 5.2. Radiolabeling of the conjugates with 64Cu in HEPES buffer (pH 7.2) at 37 °C afforded a molar activity of up to 20 μCi/μg (110 MBq/nmol). Binding was specific to the HER2 receptor, and uptake was observed for each conjugate. In mice bearing HER2+ BT-474 xenografts, PET imaging studies showed significantly higher tumor uptake, with a tumor standardized uptake value (SUV) of 0.95 ± 0.08 versus 0.38 ± 0.12 in the HER2- MDA-MB-468 xenograft control group at 24 h post-injection. PorTraz conjugates showed tumor SUV results of 1.25 ± 0.31 for n = 2.3 porphyrin chelators per antibody and 0.59 ± 0.20 for n = 5.2 porphyrin chelators per antibody. In summary, a series of porphyrin-trastuzumab conjugates were synthesized and labeled with 64Cu, displayed high binding to HER2+ cells, and illustrated uptake in mouse tumor xenografts observable by PET/CT imaging.
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BibTeX
@article{lawing2026designer,
title = {{Designer ⁶⁴Cu Porphyrin-Trastuzumab Conjugates for Imaging of HER2-Positive Breast Cancer.}},
author = {Peter C Lawing and Hailey A Houson and Zhiyuan Wu and Quang-Thien Ngo and Jonathan S Lindsey and Suzanne E Lapi},
journal = {Chemical \& biomedical imaging},
year = {2026},
month = jun,
doi = {10.1021/cbmi.6c00024},
url = {https://europepmc.org/article/MED/42953717},
note = {CC BY},
}
RIS
TY - JOUR
TI - Designer ⁶⁴Cu Porphyrin-Trastuzumab Conjugates for Imaging of HER2-Positive Breast Cancer.
AU - Peter C Lawing
AU - Hailey A Houson
AU - Zhiyuan Wu
AU - Quang-Thien Ngo
AU - Jonathan S Lindsey
AU - Suzanne E Lapi
PY - 2026
DA - 2026/06/09
JO - Chemical & biomedical imaging
DO - 10.1021/cbmi.6c00024
UR - https://europepmc.org/article/MED/42953717
AB - The human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-30% of breast cancer cases, plays a significant role in pathogenesis, and has been used as a diagnostic indicator and therapeutic target. Herein, a bioconjugatable porphyrin chelator is described, bearing a water-solubilizing swallowtail motif that projects above and below the plane of the macrocycle. This porphyrin, in various quantities, was reacted in stochastic fashion with the lysine side chains of the anti-HER2 antibody trastuzumab to afford a series of porphyrin-trastuzumab (PorTraz) products with conjugation ratios of 2.3, 3.5, 4.1, and 5.2. Radiolabeling of the conjugates with 64Cu in HEPES buffer (pH 7.2) at 37 °C afforded a molar activity of up to 20 μCi/μg (110 MBq/nmol). Binding was specific to the HER2 receptor, and uptake was observed for each conjugate. In mice bearing HER2+ BT-474 xenografts, PET imaging studies showed significantly higher tumor uptake, with a tumor standardized uptake value (SUV) of 0.95 ± 0.08 versus 0.38 ± 0.12 in the HER2- MDA-MB-468 xenograft control group at 24 h post-injection. PorTraz conjugates showed tumor SUV results of 1.25 ± 0.31 for n = 2.3 porphyrin chelators per antibody and 0.59 ± 0.20 for n = 5.2 porphyrin chelators per antibody. In summary, a series of porphyrin-trastuzumab conjugates were synthesized and labeled with 64Cu, displayed high binding to HER2+ cells, and illustrated uptake in mouse tumor xenografts observable by PET/CT imaging.
SN - 2832-3637
ER -