Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin

Sara R.D. Gamelas; Shayla Shmuel; Cristina Simó; Alex Vanover; João P.C. Tomé; Augusto C. Tomé; Leandro M.O. Lourenço; Patrícia M.R. Pereira

doi:10.1021/acs.bioconjchem.5c00056

Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin

Sara R.D. Gamelas
, Shayla Shmuel
, Cristina Simó
, Alex Vanover
, João P.C. Tomé
, Augusto C. Tomé
, Leandro M.O. Lourenço
, Patrícia M.R. Pereira

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

Abstract

Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [⁸⁹Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.

Original language	English
Pages (from-to)	1013-1020
Number of pages	8
Journal	Bioconjugate Chemistry
Volume	36
Issue number	5
DOIs	https://doi.org/10.1021/acs.bioconjchem.5c00056
State	Published - May 21 2025

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title = "Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin",

abstract = "Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [89Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9\% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.",

author = "Gamelas, \{Sara R.D.\} and Shayla Shmuel and Cristina Sim{\'o} and Alex Vanover and Tom{\'e}, \{Jo{\~a}o P.C.\} and Tom{\'e}, \{Augusto C.\} and Louren{\c c}o, \{Leandro M.O.\} and Pereira, \{Patr{\'i}cia M.R.\}",

note = "Publisher Copyright: {\textcopyright} 2025 American Chemical Society.",

year = "2025",

month = may,

day = "21",

doi = "10.1021/acs.bioconjchem.5c00056",

language = "English",

volume = "36",

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T1 - Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin

AU - Gamelas, Sara R.D.

AU - Shmuel, Shayla

AU - Simó, Cristina

AU - Vanover, Alex

AU - Tomé, João P.C.

AU - Tomé, Augusto C.

AU - Lourenço, Leandro M.O.

AU - Pereira, Patrícia M.R.

PY - 2025/5/21

Y1 - 2025/5/21

N2 - Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [89Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.

AB - Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [89Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.

UR - https://www.scopus.com/pages/publications/105004930973

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SN - 1043-1802

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JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 5

ER -

Positron Emission Tomography and Optical Imaging to Monitor Bioorthogonal Diels-Alder Click Chemistry of Trastuzumab with a Porphyrin

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