Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

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Standard

Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma. / Persson, Morten; Nedergaard, Mette K; Brandt-Larsen, Malene; Skovgaard, Dorthe; Jørgensen, Jesper T; Michaelsen, Signe R; Madsen, Jacob; Lassen, Ulrik; Poulsen, Hans S; Kjaer, Andreas.

I: Journal of Nuclear Medicine, Bind 57, Nr. 2, 02.2016, s. 272-278.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Persson, M, Nedergaard, MK, Brandt-Larsen, M, Skovgaard, D, Jørgensen, JT, Michaelsen, SR, Madsen, J, Lassen, U, Poulsen, HS & Kjaer, A 2016, 'Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma', Journal of Nuclear Medicine, bind 57, nr. 2, s. 272-278. https://doi.org/10.2967/jnumed.115.161703

APA

Persson, M., Nedergaard, M. K., Brandt-Larsen, M., Skovgaard, D., Jørgensen, J. T., Michaelsen, S. R., Madsen, J., Lassen, U., Poulsen, H. S., & Kjaer, A. (2016). Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma. Journal of Nuclear Medicine, 57(2), 272-278. https://doi.org/10.2967/jnumed.115.161703

Vancouver

Persson M, Nedergaard MK, Brandt-Larsen M, Skovgaard D, Jørgensen JT, Michaelsen SR o.a. Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma. Journal of Nuclear Medicine. 2016 feb.;57(2):272-278. https://doi.org/10.2967/jnumed.115.161703

Author

Persson, Morten ; Nedergaard, Mette K ; Brandt-Larsen, Malene ; Skovgaard, Dorthe ; Jørgensen, Jesper T ; Michaelsen, Signe R ; Madsen, Jacob ; Lassen, Ulrik ; Poulsen, Hans S ; Kjaer, Andreas. / Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma. I: Journal of Nuclear Medicine. 2016 ; Bind 57, Nr. 2. s. 272-278.

Bibtex

@article{22da32d0db064e1aa58781253b584464,
title = "Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma",
abstract = "UNLABELLED: Glioblastoma is one of the most malignant types of human cancer, and the prognosis is poor. The development and validation of novel molecular imaging biomarkers has the potential to improve tumor detection, grading, risk stratification, and treatment monitoring of gliomas. The aim of this study was to explore the potential of PET imaging of the urokinase-type plasminogen activator receptor (uPAR) in glioblastoma.METHODS: The uPAR messenger RNA expression of tumors from 19 glioblastoma patients was analyzed, and a cell culture derived from one of these patients was used to establish an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET). One MRI scan was obtained for each mouse to confirm tumor location. The uPAR specificity of (64)Cu-NOTA-AE105 was confirmed by alignment of hematoxylin- and eosin-stained and uPAR immunohistochemistry-stained slides of the brain with the activity distribution as determined using autoradiography.RESULTS: uPAR expression was found in all 19 glioblastoma patient tumors, and high expression of uPAR correlated with decreased overall survival (P = 0.04). Radiolabeling of NOTA-AE105 with (64)Cu and (68)Ga was straightforward, resulting in a specific activity of approximately 20 GBq/μmol and a radiochemical purity of more than 98% for (64)Cu-NOTA-AE105 and more than 97% for (68)Ga-NOTA-AE105. High image contrast resulting in clear tumor delineation was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105. Absolute uptake in tumor was higher for (18)F-FET (3.5 ± 0.8 percentage injected dose [%ID]/g) than for (64)Cu-NOTA-AE105 (1.2 ± 0.4 %ID/g) or (68)Ga-NOTA-AE105 (0.4 ± 0.1 %ID/g). A similar pattern was observed in background brain tissue, where uptake was 1.9 ± 0.1 %ID/g for (18)F-fluorothymidine, compared with 0.05 ± 0.01 %ID/g for (68)Ga-NOTA-AE105 and 0.11 ± 0.02 %ID/g for (64)Cu-NOTA-AE105. The result was a significantly higher tumor-to-background ratio for both (68)Ga-NOTA-AE105 (7.6 ± 2.1, P < 0.05) and (64)Cu-NOTA-AE105 (10.6 ± 2.3, P < 0.01) than for (18)F-FET PET (1.8 ± 0.3). Autoradiography of brain slides confirmed that the accumulation of (64)Cu-NOTA-AE105 corresponded well with uPAR-positive cancer cells.CONCLUSION: On the basis of our translational study, uPAR PET may be a highly promising imaging biomarker for glioblastoma. Further clinical exploration of uPAR PET in glioblastoma is therefore justified.",
keywords = "Adult, Animals, Autoradiography, Biomarkers, Tumor, Brain Neoplasms, Cells, Cultured, Copper Radioisotopes, Female, Glioblastoma, Humans, Male, Mice, Middle Aged, Positron-Emission Tomography, RNA, Messenger, Radiopharmaceuticals, Receptors, Survival Analysis, Xenograft Model Antitumor Assays, Urokinase Plasminogen Activator",
author = "Morten Persson and Nedergaard, {Mette K} and Malene Brandt-Larsen and Dorthe Skovgaard and J{\o}rgensen, {Jesper T} and Michaelsen, {Signe R} and Jacob Madsen and Ulrik Lassen and Poulsen, {Hans S} and Andreas Kjaer",
note = "{\textcopyright} 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2016",
month = feb,
doi = "10.2967/jnumed.115.161703",
language = "English",
volume = "57",
pages = "272--278",
journal = "The Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine",
number = "2",

}

RIS

TY - JOUR

T1 - Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

AU - Persson, Morten

AU - Nedergaard, Mette K

AU - Brandt-Larsen, Malene

AU - Skovgaard, Dorthe

AU - Jørgensen, Jesper T

AU - Michaelsen, Signe R

AU - Madsen, Jacob

AU - Lassen, Ulrik

AU - Poulsen, Hans S

AU - Kjaer, Andreas

N1 - © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2016/2

Y1 - 2016/2

N2 - UNLABELLED: Glioblastoma is one of the most malignant types of human cancer, and the prognosis is poor. The development and validation of novel molecular imaging biomarkers has the potential to improve tumor detection, grading, risk stratification, and treatment monitoring of gliomas. The aim of this study was to explore the potential of PET imaging of the urokinase-type plasminogen activator receptor (uPAR) in glioblastoma.METHODS: The uPAR messenger RNA expression of tumors from 19 glioblastoma patients was analyzed, and a cell culture derived from one of these patients was used to establish an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET). One MRI scan was obtained for each mouse to confirm tumor location. The uPAR specificity of (64)Cu-NOTA-AE105 was confirmed by alignment of hematoxylin- and eosin-stained and uPAR immunohistochemistry-stained slides of the brain with the activity distribution as determined using autoradiography.RESULTS: uPAR expression was found in all 19 glioblastoma patient tumors, and high expression of uPAR correlated with decreased overall survival (P = 0.04). Radiolabeling of NOTA-AE105 with (64)Cu and (68)Ga was straightforward, resulting in a specific activity of approximately 20 GBq/μmol and a radiochemical purity of more than 98% for (64)Cu-NOTA-AE105 and more than 97% for (68)Ga-NOTA-AE105. High image contrast resulting in clear tumor delineation was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105. Absolute uptake in tumor was higher for (18)F-FET (3.5 ± 0.8 percentage injected dose [%ID]/g) than for (64)Cu-NOTA-AE105 (1.2 ± 0.4 %ID/g) or (68)Ga-NOTA-AE105 (0.4 ± 0.1 %ID/g). A similar pattern was observed in background brain tissue, where uptake was 1.9 ± 0.1 %ID/g for (18)F-fluorothymidine, compared with 0.05 ± 0.01 %ID/g for (68)Ga-NOTA-AE105 and 0.11 ± 0.02 %ID/g for (64)Cu-NOTA-AE105. The result was a significantly higher tumor-to-background ratio for both (68)Ga-NOTA-AE105 (7.6 ± 2.1, P < 0.05) and (64)Cu-NOTA-AE105 (10.6 ± 2.3, P < 0.01) than for (18)F-FET PET (1.8 ± 0.3). Autoradiography of brain slides confirmed that the accumulation of (64)Cu-NOTA-AE105 corresponded well with uPAR-positive cancer cells.CONCLUSION: On the basis of our translational study, uPAR PET may be a highly promising imaging biomarker for glioblastoma. Further clinical exploration of uPAR PET in glioblastoma is therefore justified.

AB - UNLABELLED: Glioblastoma is one of the most malignant types of human cancer, and the prognosis is poor. The development and validation of novel molecular imaging biomarkers has the potential to improve tumor detection, grading, risk stratification, and treatment monitoring of gliomas. The aim of this study was to explore the potential of PET imaging of the urokinase-type plasminogen activator receptor (uPAR) in glioblastoma.METHODS: The uPAR messenger RNA expression of tumors from 19 glioblastoma patients was analyzed, and a cell culture derived from one of these patients was used to establish an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET). One MRI scan was obtained for each mouse to confirm tumor location. The uPAR specificity of (64)Cu-NOTA-AE105 was confirmed by alignment of hematoxylin- and eosin-stained and uPAR immunohistochemistry-stained slides of the brain with the activity distribution as determined using autoradiography.RESULTS: uPAR expression was found in all 19 glioblastoma patient tumors, and high expression of uPAR correlated with decreased overall survival (P = 0.04). Radiolabeling of NOTA-AE105 with (64)Cu and (68)Ga was straightforward, resulting in a specific activity of approximately 20 GBq/μmol and a radiochemical purity of more than 98% for (64)Cu-NOTA-AE105 and more than 97% for (68)Ga-NOTA-AE105. High image contrast resulting in clear tumor delineation was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105. Absolute uptake in tumor was higher for (18)F-FET (3.5 ± 0.8 percentage injected dose [%ID]/g) than for (64)Cu-NOTA-AE105 (1.2 ± 0.4 %ID/g) or (68)Ga-NOTA-AE105 (0.4 ± 0.1 %ID/g). A similar pattern was observed in background brain tissue, where uptake was 1.9 ± 0.1 %ID/g for (18)F-fluorothymidine, compared with 0.05 ± 0.01 %ID/g for (68)Ga-NOTA-AE105 and 0.11 ± 0.02 %ID/g for (64)Cu-NOTA-AE105. The result was a significantly higher tumor-to-background ratio for both (68)Ga-NOTA-AE105 (7.6 ± 2.1, P < 0.05) and (64)Cu-NOTA-AE105 (10.6 ± 2.3, P < 0.01) than for (18)F-FET PET (1.8 ± 0.3). Autoradiography of brain slides confirmed that the accumulation of (64)Cu-NOTA-AE105 corresponded well with uPAR-positive cancer cells.CONCLUSION: On the basis of our translational study, uPAR PET may be a highly promising imaging biomarker for glioblastoma. Further clinical exploration of uPAR PET in glioblastoma is therefore justified.

KW - Adult

KW - Animals

KW - Autoradiography

KW - Biomarkers, Tumor

KW - Brain Neoplasms

KW - Cells, Cultured

KW - Copper Radioisotopes

KW - Female

KW - Glioblastoma

KW - Humans

KW - Male

KW - Mice

KW - Middle Aged

KW - Positron-Emission Tomography

KW - RNA, Messenger

KW - Radiopharmaceuticals

KW - Receptors

KW - Survival Analysis

KW - Xenograft Model Antitumor Assays

KW - Urokinase Plasminogen Activator

U2 - 10.2967/jnumed.115.161703

DO - 10.2967/jnumed.115.161703

M3 - Journal article

C2 - 26429955

VL - 57

SP - 272

EP - 278

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

SN - 0161-5505

IS - 2

ER -

ID: 164441424