68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers. / Persson, Morten; Madsen, Jacob; Østergaard, Søren; Ploug, Michael; Kjaer, Andreas.

I: Nuclear Medicine and Biology, Bind 39, Nr. 4, 05.2012, s. 560-569.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Persson, M, Madsen, J, Østergaard, S, Ploug, M & Kjaer, A 2012, '68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers', Nuclear Medicine and Biology, bind 39, nr. 4, s. 560-569. https://doi.org/10.1016/j.nucmedbio.2011.10.011

APA

Persson, M., Madsen, J., Østergaard, S., Ploug, M., & Kjaer, A. (2012). 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers. Nuclear Medicine and Biology, 39(4), 560-569. https://doi.org/10.1016/j.nucmedbio.2011.10.011

Vancouver

Persson M, Madsen J, Østergaard S, Ploug M, Kjaer A. 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers. Nuclear Medicine and Biology. 2012 maj;39(4):560-569. https://doi.org/10.1016/j.nucmedbio.2011.10.011

Author

Persson, Morten ; Madsen, Jacob ; Østergaard, Søren ; Ploug, Michael ; Kjaer, Andreas. / 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers. I: Nuclear Medicine and Biology. 2012 ; Bind 39, Nr. 4. s. 560-569.

Bibtex

@article{ac81415b3c6d47afa1bed2380c66137c,
title = "68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers",
abstract = "INTRODUCTION: The urokinase-type plasminogen activator receptor (uPAR) is a well-established biomarker for tumor aggressiveness and metastatic potential. DOTA-AE105 and DOTA-AE105-NH(2) labeled with (64)Cu have previously been demonstrated to be able to noninvasively monitor uPAR expression using positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce (68)Ga-DOTA-AE105-NH(2) and (68)Ga-NODAGA-AE105-NH(2) and evaluate their imaging properties using small-animal PET. METHODS: Synthesis of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) was based on solid-phase peptide synthesis protocols using the Fmoc strategy. (68)GaCl(3) was eluted from a (68)Ge/(68)Ga generator. The eluate was either concentrated on a cation-exchange column or fractionated and used directly for labeling. For in vitro characterization of both tracers, partition coefficient, buffer and plasma stability, uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft. RESULTS: In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated peptides and identical to AE105. Labeling of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) with (68)Ga was done at 95°C and room temperature, respectively. The highest radiochemical yield and purity were obtained using fractionated elution, whereas a negative effect of acetone on labeling efficiency for NODAGA-AE105-NH(2) was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min postinjection and 2.0% ID/g and 1.1% ID/g 60 min postinjection for (68)Ga-NODAGA-AE105-NH(2) and (68)Ga-DOTA-AE105-NH(2), respectively. A significantly higher tumor-to-muscle ratio (P",
keywords = "Acetates, Amides, Animals, Cell Line, Tumor, Cell Transformation, Neoplastic, Chelating Agents, Drug Stability, Female, Gallium, Gallium Radioisotopes, Glioma, Heterocyclic Compounds, 1-Ring, Humans, Mice, Neoplasm Invasiveness, Peptides, Positron-Emission Tomography, Protein Binding, Receptors, Urokinase Plasminogen Activator",
author = "Morten Persson and Jacob Madsen and S{\o}ren {\O}stergaard and Michael Ploug and Andreas Kjaer",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
month = may,
doi = "10.1016/j.nucmedbio.2011.10.011",
language = "English",
volume = "39",
pages = "560--569",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - 68Ga-labeling and in vivo evaluation of a uPAR binding DOTA- and NODAGA-conjugated peptide for PET imaging of invasive cancers

AU - Persson, Morten

AU - Madsen, Jacob

AU - Østergaard, Søren

AU - Ploug, Michael

AU - Kjaer, Andreas

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/5

Y1 - 2012/5

N2 - INTRODUCTION: The urokinase-type plasminogen activator receptor (uPAR) is a well-established biomarker for tumor aggressiveness and metastatic potential. DOTA-AE105 and DOTA-AE105-NH(2) labeled with (64)Cu have previously been demonstrated to be able to noninvasively monitor uPAR expression using positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce (68)Ga-DOTA-AE105-NH(2) and (68)Ga-NODAGA-AE105-NH(2) and evaluate their imaging properties using small-animal PET. METHODS: Synthesis of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) was based on solid-phase peptide synthesis protocols using the Fmoc strategy. (68)GaCl(3) was eluted from a (68)Ge/(68)Ga generator. The eluate was either concentrated on a cation-exchange column or fractionated and used directly for labeling. For in vitro characterization of both tracers, partition coefficient, buffer and plasma stability, uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft. RESULTS: In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated peptides and identical to AE105. Labeling of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) with (68)Ga was done at 95°C and room temperature, respectively. The highest radiochemical yield and purity were obtained using fractionated elution, whereas a negative effect of acetone on labeling efficiency for NODAGA-AE105-NH(2) was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min postinjection and 2.0% ID/g and 1.1% ID/g 60 min postinjection for (68)Ga-NODAGA-AE105-NH(2) and (68)Ga-DOTA-AE105-NH(2), respectively. A significantly higher tumor-to-muscle ratio (P

AB - INTRODUCTION: The urokinase-type plasminogen activator receptor (uPAR) is a well-established biomarker for tumor aggressiveness and metastatic potential. DOTA-AE105 and DOTA-AE105-NH(2) labeled with (64)Cu have previously been demonstrated to be able to noninvasively monitor uPAR expression using positron emission tomography (PET) in human cancer xenograft mice models. Here we introduce (68)Ga-DOTA-AE105-NH(2) and (68)Ga-NODAGA-AE105-NH(2) and evaluate their imaging properties using small-animal PET. METHODS: Synthesis of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) was based on solid-phase peptide synthesis protocols using the Fmoc strategy. (68)GaCl(3) was eluted from a (68)Ge/(68)Ga generator. The eluate was either concentrated on a cation-exchange column or fractionated and used directly for labeling. For in vitro characterization of both tracers, partition coefficient, buffer and plasma stability, uPAR binding affinity and cell uptake were determined. To characterize the in vivo properties, dynamic microPET imaging was carried out in nude mice bearing human glioma U87MG tumor xenograft. RESULTS: In vitro experiments revealed uPAR binding affinities in the lower nM range for both conjugated peptides and identical to AE105. Labeling of DOTA-AE105-NH(2) and NODAGA-AE105-NH(2) with (68)Ga was done at 95°C and room temperature, respectively. The highest radiochemical yield and purity were obtained using fractionated elution, whereas a negative effect of acetone on labeling efficiency for NODAGA-AE105-NH(2) was observed. Good stability in phosphate-buffered saline and mouse plasma was observed. High cell uptake was found for both tracers in U87MG tumor cells. Dynamic microPET imaging demonstrated good tumor-to-background ratio for both tracers. Tumor uptake was 2.1% ID/g and 1.3% ID/g 30 min postinjection and 2.0% ID/g and 1.1% ID/g 60 min postinjection for (68)Ga-NODAGA-AE105-NH(2) and (68)Ga-DOTA-AE105-NH(2), respectively. A significantly higher tumor-to-muscle ratio (P

KW - Acetates

KW - Amides

KW - Animals

KW - Cell Line, Tumor

KW - Cell Transformation, Neoplastic

KW - Chelating Agents

KW - Drug Stability

KW - Female

KW - Gallium

KW - Gallium Radioisotopes

KW - Glioma

KW - Heterocyclic Compounds, 1-Ring

KW - Humans

KW - Mice

KW - Neoplasm Invasiveness

KW - Peptides

KW - Positron-Emission Tomography

KW - Protein Binding

KW - Receptors, Urokinase Plasminogen Activator

U2 - 10.1016/j.nucmedbio.2011.10.011

DO - 10.1016/j.nucmedbio.2011.10.011

M3 - Journal article

C2 - 22172391

VL - 39

SP - 560

EP - 569

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 4

ER -

ID: 40215591