Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)

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Standard

Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR). / Loft, Mathias Dyrberg; Sun, Yao; Liu, Changhao; Christensen, Camilla; Huang, Daijuan; Kjaer, Andreas; Cheng, Zhen.

I: Amino Acids, Bind 49, Nr. 6, 2017, s. 1089-1100.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Loft, MD, Sun, Y, Liu, C, Christensen, C, Huang, D, Kjaer, A & Cheng, Z 2017, 'Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)', Amino Acids, bind 49, nr. 6, s. 1089-1100. https://doi.org/10.1007/s00726-017-2407-4

APA

Loft, M. D., Sun, Y., Liu, C., Christensen, C., Huang, D., Kjaer, A., & Cheng, Z. (2017). Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR). Amino Acids, 49(6), 1089-1100. https://doi.org/10.1007/s00726-017-2407-4

Vancouver

Loft MD, Sun Y, Liu C, Christensen C, Huang D, Kjaer A o.a. Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR). Amino Acids. 2017;49(6):1089-1100. https://doi.org/10.1007/s00726-017-2407-4

Author

Loft, Mathias Dyrberg ; Sun, Yao ; Liu, Changhao ; Christensen, Camilla ; Huang, Daijuan ; Kjaer, Andreas ; Cheng, Zhen. / Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR). I: Amino Acids. 2017 ; Bind 49, Nr. 6. s. 1089-1100.

Bibtex

@article{ef6682f469a14b3ab829277c58978fea,
title = "Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)",
abstract = "The urokinase-type plasminogen activator receptor (uPAR) is overexpressed in several cancers including glioblastoma (GBM) and is an established biomarker for metastatic potential. The uPAR-targeting peptide AE105-NH2(Ac-Asp-Cha-Phe-(D)Ser-(D)Arg-Tyr-Leu-Trp-Ser-CONH2) is a promising candidate for non-invasive positron emission tomography (PET) imaging of uPAR. Despite the optimal physical properties of68Ga for peptide-based PET imaging, low tumor uptakes have previously been reported using68Ga-labeled AE105-NH2-based tracers. In an attempt to optimize the tumor uptake, we developed three novel tracers with alkane (AOC) and polyethylene glycol (PEG) spacers inserted between AE105-NH2and the radio metal chelator 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA). The resulting tracers NODAGA-AOC-AE105-NH2, NODAGA-PEG3-AE105-NH2and NODAGA-PEG8-AE105-NH2were compared to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled the in vivo tumor uptake after 1 h compared with the non-spacer version:68Ga-NODAGA-PEG3-AE105-NH2(2.08 ± 0.37%ID/g) and68Ga-NODAGA-PEG8-AE105-NH2(2.01 ± 0.22%ID/g) vs.68Ga-NODAGA-AE105-NH2(0.70 ± 0.40%ID/g), p < 0.05. In addition,68Ga-NODAGA-PEG8-AE105-NH2showed significantly higher (p < 0.05) tumor-to-background contrast (3.68 ± 0.23) than the other tracers. The specific tumor-targeting property of68Ga-NODAGA-PEG8-AE105-NH2was established by effectively blocking the tumor uptake with co-injection of unlabeled AE105-NH2(1 h: unblocked 2.01 ± 0.22%ID/g vs. blocked 1.24 ± 0.09%ID/g, p < 0.05). Ex vivo biodistribution confirmed the improved tumor uptakes of the PEG-modified tracers.68Ga-NODAGA-PEG8-AE105-NH2is thus a promising candidate for human translation for PET imaging of GBM.",
keywords = "Cell Line, Tumor, Contrast Media/chemistry, Gallium/chemistry, Glioblastoma/diagnostic imaging, Humans, Peptides/chemistry, Positron-Emission Tomography, Receptors, Urokinase Plasminogen Activator/agonists",
author = "Loft, {Mathias Dyrberg} and Yao Sun and Changhao Liu and Camilla Christensen and Daijuan Huang and Andreas Kjaer and Zhen Cheng",
year = "2017",
doi = "10.1007/s00726-017-2407-4",
language = "English",
volume = "49",
pages = "1089--1100",
journal = "Amino Acids",
issn = "0939-4451",
publisher = "Springer Wien",
number = "6",

}

RIS

TY - JOUR

T1 - Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)

AU - Loft, Mathias Dyrberg

AU - Sun, Yao

AU - Liu, Changhao

AU - Christensen, Camilla

AU - Huang, Daijuan

AU - Kjaer, Andreas

AU - Cheng, Zhen

PY - 2017

Y1 - 2017

N2 - The urokinase-type plasminogen activator receptor (uPAR) is overexpressed in several cancers including glioblastoma (GBM) and is an established biomarker for metastatic potential. The uPAR-targeting peptide AE105-NH2(Ac-Asp-Cha-Phe-(D)Ser-(D)Arg-Tyr-Leu-Trp-Ser-CONH2) is a promising candidate for non-invasive positron emission tomography (PET) imaging of uPAR. Despite the optimal physical properties of68Ga for peptide-based PET imaging, low tumor uptakes have previously been reported using68Ga-labeled AE105-NH2-based tracers. In an attempt to optimize the tumor uptake, we developed three novel tracers with alkane (AOC) and polyethylene glycol (PEG) spacers inserted between AE105-NH2and the radio metal chelator 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA). The resulting tracers NODAGA-AOC-AE105-NH2, NODAGA-PEG3-AE105-NH2and NODAGA-PEG8-AE105-NH2were compared to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled the in vivo tumor uptake after 1 h compared with the non-spacer version:68Ga-NODAGA-PEG3-AE105-NH2(2.08 ± 0.37%ID/g) and68Ga-NODAGA-PEG8-AE105-NH2(2.01 ± 0.22%ID/g) vs.68Ga-NODAGA-AE105-NH2(0.70 ± 0.40%ID/g), p < 0.05. In addition,68Ga-NODAGA-PEG8-AE105-NH2showed significantly higher (p < 0.05) tumor-to-background contrast (3.68 ± 0.23) than the other tracers. The specific tumor-targeting property of68Ga-NODAGA-PEG8-AE105-NH2was established by effectively blocking the tumor uptake with co-injection of unlabeled AE105-NH2(1 h: unblocked 2.01 ± 0.22%ID/g vs. blocked 1.24 ± 0.09%ID/g, p < 0.05). Ex vivo biodistribution confirmed the improved tumor uptakes of the PEG-modified tracers.68Ga-NODAGA-PEG8-AE105-NH2is thus a promising candidate for human translation for PET imaging of GBM.

AB - The urokinase-type plasminogen activator receptor (uPAR) is overexpressed in several cancers including glioblastoma (GBM) and is an established biomarker for metastatic potential. The uPAR-targeting peptide AE105-NH2(Ac-Asp-Cha-Phe-(D)Ser-(D)Arg-Tyr-Leu-Trp-Ser-CONH2) is a promising candidate for non-invasive positron emission tomography (PET) imaging of uPAR. Despite the optimal physical properties of68Ga for peptide-based PET imaging, low tumor uptakes have previously been reported using68Ga-labeled AE105-NH2-based tracers. In an attempt to optimize the tumor uptake, we developed three novel tracers with alkane (AOC) and polyethylene glycol (PEG) spacers inserted between AE105-NH2and the radio metal chelator 2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA). The resulting tracers NODAGA-AOC-AE105-NH2, NODAGA-PEG3-AE105-NH2and NODAGA-PEG8-AE105-NH2were compared to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled the in vivo tumor uptake after 1 h compared with the non-spacer version:68Ga-NODAGA-PEG3-AE105-NH2(2.08 ± 0.37%ID/g) and68Ga-NODAGA-PEG8-AE105-NH2(2.01 ± 0.22%ID/g) vs.68Ga-NODAGA-AE105-NH2(0.70 ± 0.40%ID/g), p < 0.05. In addition,68Ga-NODAGA-PEG8-AE105-NH2showed significantly higher (p < 0.05) tumor-to-background contrast (3.68 ± 0.23) than the other tracers. The specific tumor-targeting property of68Ga-NODAGA-PEG8-AE105-NH2was established by effectively blocking the tumor uptake with co-injection of unlabeled AE105-NH2(1 h: unblocked 2.01 ± 0.22%ID/g vs. blocked 1.24 ± 0.09%ID/g, p < 0.05). Ex vivo biodistribution confirmed the improved tumor uptakes of the PEG-modified tracers.68Ga-NODAGA-PEG8-AE105-NH2is thus a promising candidate for human translation for PET imaging of GBM.

KW - Cell Line, Tumor

KW - Contrast Media/chemistry

KW - Gallium/chemistry

KW - Glioblastoma/diagnostic imaging

KW - Humans

KW - Peptides/chemistry

KW - Positron-Emission Tomography

KW - Receptors, Urokinase Plasminogen Activator/agonists

U2 - 10.1007/s00726-017-2407-4

DO - 10.1007/s00726-017-2407-4

M3 - Journal article

C2 - 28316028

VL - 49

SP - 1089

EP - 1100

JO - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 6

ER -

ID: 194042628