Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging

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Standard

Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging. / Müller, Marius; Shalgunov, Vladimir; Hvass, Lars; Jørgensen, Jesper T.; Kramer, Vasko; Staudt, Markus; Battisti, Umberto Maria; Kjaer, Andreas; Herth, Matthias M.

I: Bioorganic and Medicinal Chemistry Letters, Bind 80, 129088, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Müller, M, Shalgunov, V, Hvass, L, Jørgensen, JT, Kramer, V, Staudt, M, Battisti, UM, Kjaer, A & Herth, MM 2023, 'Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging', Bioorganic and Medicinal Chemistry Letters, bind 80, 129088. https://doi.org/10.1016/j.bmcl.2022.129088

APA

Müller, M., Shalgunov, V., Hvass, L., Jørgensen, J. T., Kramer, V., Staudt, M., Battisti, U. M., Kjaer, A., & Herth, M. M. (2023). Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging. Bioorganic and Medicinal Chemistry Letters, 80, [129088]. https://doi.org/10.1016/j.bmcl.2022.129088

Vancouver

Müller M, Shalgunov V, Hvass L, Jørgensen JT, Kramer V, Staudt M o.a. Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging. Bioorganic and Medicinal Chemistry Letters. 2023;80. 129088. https://doi.org/10.1016/j.bmcl.2022.129088

Author

Müller, Marius ; Shalgunov, Vladimir ; Hvass, Lars ; Jørgensen, Jesper T. ; Kramer, Vasko ; Staudt, Markus ; Battisti, Umberto Maria ; Kjaer, Andreas ; Herth, Matthias M. / Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging. I: Bioorganic and Medicinal Chemistry Letters. 2023 ; Bind 80.

Bibtex

@article{2495693dab344093bdb5d0ccf004a69e,
title = "Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging",
abstract = "Tucatinib is a selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) in April 2020 for HER2-positive lesions in metastatic breast cancer patients, including CNS metastases. In this article, we attempted to develop the first small molecule, blood–brain-barrier (BBB) penetrant HER2 PET imaging probe based on tucatinib. [11C]tucatinib was synthesized via a Stille-coupling from the respective trimethylstannyl precursor and its biodistribution was evaluated in NMRI nude mice bearing HER2-overexpressing human ovarian cancer cells (SKOV-3). No significant tumor accumulation was observed despite its high affinity for HER-2 receptors (IC50 = 6.9 nM). High liver and intestinal uptake indicate that [11C]tucatinib is too lipophilic to be used as a tumor targeting PET tracer. Therefore, chemical modifications of [11C]tucatinib are needed to increase the polarity for tumor imaging. Tucatinib as an FDA approved drug is still an interesting platform to develop the first small molecule HER2-selective PET tracer. The study highlights the differences between a drug, which needs to be effective, and an imaging agent, which is dependent on contrast.",
keywords = "Breast cancer, Carbon-11, HER2, PET imaging, Radiolabeling, Tucatinib",
author = "Marius M{\"u}ller and Vladimir Shalgunov and Lars Hvass and J{\o}rgensen, {Jesper T.} and Vasko Kramer and Markus Staudt and Battisti, {Umberto Maria} and Andreas Kjaer and Herth, {Matthias M.}",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2023",
doi = "10.1016/j.bmcl.2022.129088",
language = "English",
volume = "80",
journal = "Bioorganic & Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging

AU - Müller, Marius

AU - Shalgunov, Vladimir

AU - Hvass, Lars

AU - Jørgensen, Jesper T.

AU - Kramer, Vasko

AU - Staudt, Markus

AU - Battisti, Umberto Maria

AU - Kjaer, Andreas

AU - Herth, Matthias M.

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2023

Y1 - 2023

N2 - Tucatinib is a selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) in April 2020 for HER2-positive lesions in metastatic breast cancer patients, including CNS metastases. In this article, we attempted to develop the first small molecule, blood–brain-barrier (BBB) penetrant HER2 PET imaging probe based on tucatinib. [11C]tucatinib was synthesized via a Stille-coupling from the respective trimethylstannyl precursor and its biodistribution was evaluated in NMRI nude mice bearing HER2-overexpressing human ovarian cancer cells (SKOV-3). No significant tumor accumulation was observed despite its high affinity for HER-2 receptors (IC50 = 6.9 nM). High liver and intestinal uptake indicate that [11C]tucatinib is too lipophilic to be used as a tumor targeting PET tracer. Therefore, chemical modifications of [11C]tucatinib are needed to increase the polarity for tumor imaging. Tucatinib as an FDA approved drug is still an interesting platform to develop the first small molecule HER2-selective PET tracer. The study highlights the differences between a drug, which needs to be effective, and an imaging agent, which is dependent on contrast.

AB - Tucatinib is a selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) in April 2020 for HER2-positive lesions in metastatic breast cancer patients, including CNS metastases. In this article, we attempted to develop the first small molecule, blood–brain-barrier (BBB) penetrant HER2 PET imaging probe based on tucatinib. [11C]tucatinib was synthesized via a Stille-coupling from the respective trimethylstannyl precursor and its biodistribution was evaluated in NMRI nude mice bearing HER2-overexpressing human ovarian cancer cells (SKOV-3). No significant tumor accumulation was observed despite its high affinity for HER-2 receptors (IC50 = 6.9 nM). High liver and intestinal uptake indicate that [11C]tucatinib is too lipophilic to be used as a tumor targeting PET tracer. Therefore, chemical modifications of [11C]tucatinib are needed to increase the polarity for tumor imaging. Tucatinib as an FDA approved drug is still an interesting platform to develop the first small molecule HER2-selective PET tracer. The study highlights the differences between a drug, which needs to be effective, and an imaging agent, which is dependent on contrast.

KW - Breast cancer

KW - Carbon-11

KW - HER2

KW - PET imaging

KW - Radiolabeling

KW - Tucatinib

U2 - 10.1016/j.bmcl.2022.129088

DO - 10.1016/j.bmcl.2022.129088

M3 - Journal article

C2 - 36455802

AN - SCOPUS:85143536861

VL - 80

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

M1 - 129088

ER -

ID: 331782506