Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue

Mattia Asti, Michele Iori, Pier C. Capponi, Giulia Atti, Sara Rubagotti, René Martin, Albert Brennauer, Marco Müller, Ralf Bergmann, Paola A. Erba, Annibale Versari

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and breast cancer, but the influence of different chelators, which differ in terms of radiochemical reactivity and stability, have not been explored so far. In order to find the best suitable chelator for labelling of AMBA, we synthesized AMBA analogues linked to the most commonly used chelators DOTA, NOTA and NODAGA and compared their reactivity and stability after labelling with 68-Gallium. Methods: For the synthesis of DO3A-, NO2A- and NODAGA-AMBA, a solid-phase synthesis approach was used. The influence of concentration, pH and temperature on the radiolabelling was analysed. The in vitro stability of all complexes in saline, human serum, human whole blood and against transchelation and transmetallation was analysed. Results: The peptides were synthesised in high yield and purity. Purity and identity of products and impurities were confirmed using UHPLC coupled to ESI-MS. Radiolabelling of these peptides was optimal at elevated temperature, although room temperature labelling was reported previously for NOTA and NODAGA chelators. The highest reactivity was observed for NODAGA-AMBA. On preparation of NO2A-AMBA, the formation of a by-product was detected with HPLC. More detailed analysis revealed the formation of an isomer with the same mass to charge ratio which led to the conclusion that a coordination isomer was formed. All complexes showed high stability in saline, human serum or when challenged with DTPA, transferrin and varying metals (Fe3+, Cu2+, Zn2+). Conversely, the stability in human blood was low, and varying metabolites were detected and identified by ESI-MS. Conclusion: All three precursors are available in high yields suitable for routine production. NODAGA-AMBA showed the most favoured features when labelled with 68-gallium, but a further comparison in vivo should be performed in order to confirm the superior features found in vitro.

Original languageEnglish
Pages (from-to)24-35
Number of pages12
JournalNuclear Medicine and Biology
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Bombesin
Gallium
Chelating Agents
Temperature
Pentetic Acid
Peptides
Solid-Phase Synthesis Techniques
Transferrin
Serum
Prostatic Neoplasms
Metals
High Pressure Liquid Chromatography
1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
Breast Neoplasms

Keywords

  • Ga-labelling
  • Ga-NODAGA-AMBA
  • AMBA-chelators
  • Bombesin analogues
  • Gallium radionuclides

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue. / Asti, Mattia; Iori, Michele; Capponi, Pier C.; Atti, Giulia; Rubagotti, Sara; Martin, René; Brennauer, Albert; Müller, Marco; Bergmann, Ralf; Erba, Paola A.; Versari, Annibale.

In: Nuclear Medicine and Biology, Vol. 41, No. 1, 01.2014, p. 24-35.

Research output: Contribution to journalArticle

Asti, M, Iori, M, Capponi, PC, Atti, G, Rubagotti, S, Martin, R, Brennauer, A, Müller, M, Bergmann, R, Erba, PA & Versari, A 2014, 'Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue', Nuclear Medicine and Biology, vol. 41, no. 1, pp. 24-35. https://doi.org/10.1016/j.nucmedbio.2013.08.010
Asti, Mattia ; Iori, Michele ; Capponi, Pier C. ; Atti, Giulia ; Rubagotti, Sara ; Martin, René ; Brennauer, Albert ; Müller, Marco ; Bergmann, Ralf ; Erba, Paola A. ; Versari, Annibale. / Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue. In: Nuclear Medicine and Biology. 2014 ; Vol. 41, No. 1. pp. 24-35.
@article{abe7831671de43f080e3503782210896,
title = "Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue",
abstract = "The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and breast cancer, but the influence of different chelators, which differ in terms of radiochemical reactivity and stability, have not been explored so far. In order to find the best suitable chelator for labelling of AMBA, we synthesized AMBA analogues linked to the most commonly used chelators DOTA, NOTA and NODAGA and compared their reactivity and stability after labelling with 68-Gallium. Methods: For the synthesis of DO3A-, NO2A- and NODAGA-AMBA, a solid-phase synthesis approach was used. The influence of concentration, pH and temperature on the radiolabelling was analysed. The in vitro stability of all complexes in saline, human serum, human whole blood and against transchelation and transmetallation was analysed. Results: The peptides were synthesised in high yield and purity. Purity and identity of products and impurities were confirmed using UHPLC coupled to ESI-MS. Radiolabelling of these peptides was optimal at elevated temperature, although room temperature labelling was reported previously for NOTA and NODAGA chelators. The highest reactivity was observed for NODAGA-AMBA. On preparation of NO2A-AMBA, the formation of a by-product was detected with HPLC. More detailed analysis revealed the formation of an isomer with the same mass to charge ratio which led to the conclusion that a coordination isomer was formed. All complexes showed high stability in saline, human serum or when challenged with DTPA, transferrin and varying metals (Fe3+, Cu2+, Zn2+). Conversely, the stability in human blood was low, and varying metabolites were detected and identified by ESI-MS. Conclusion: All three precursors are available in high yields suitable for routine production. NODAGA-AMBA showed the most favoured features when labelled with 68-gallium, but a further comparison in vivo should be performed in order to confirm the superior features found in vitro.",
keywords = "Ga-labelling, Ga-NODAGA-AMBA, AMBA-chelators, Bombesin analogues, Gallium radionuclides",
author = "Mattia Asti and Michele Iori and Capponi, {Pier C.} and Giulia Atti and Sara Rubagotti and Ren{\'e} Martin and Albert Brennauer and Marco M{\"u}ller and Ralf Bergmann and Erba, {Paola A.} and Annibale Versari",
year = "2014",
month = "1",
doi = "10.1016/j.nucmedbio.2013.08.010",
language = "English",
volume = "41",
pages = "24--35",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue

AU - Asti, Mattia

AU - Iori, Michele

AU - Capponi, Pier C.

AU - Atti, Giulia

AU - Rubagotti, Sara

AU - Martin, René

AU - Brennauer, Albert

AU - Müller, Marco

AU - Bergmann, Ralf

AU - Erba, Paola A.

AU - Versari, Annibale

PY - 2014/1

Y1 - 2014/1

N2 - The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and breast cancer, but the influence of different chelators, which differ in terms of radiochemical reactivity and stability, have not been explored so far. In order to find the best suitable chelator for labelling of AMBA, we synthesized AMBA analogues linked to the most commonly used chelators DOTA, NOTA and NODAGA and compared their reactivity and stability after labelling with 68-Gallium. Methods: For the synthesis of DO3A-, NO2A- and NODAGA-AMBA, a solid-phase synthesis approach was used. The influence of concentration, pH and temperature on the radiolabelling was analysed. The in vitro stability of all complexes in saline, human serum, human whole blood and against transchelation and transmetallation was analysed. Results: The peptides were synthesised in high yield and purity. Purity and identity of products and impurities were confirmed using UHPLC coupled to ESI-MS. Radiolabelling of these peptides was optimal at elevated temperature, although room temperature labelling was reported previously for NOTA and NODAGA chelators. The highest reactivity was observed for NODAGA-AMBA. On preparation of NO2A-AMBA, the formation of a by-product was detected with HPLC. More detailed analysis revealed the formation of an isomer with the same mass to charge ratio which led to the conclusion that a coordination isomer was formed. All complexes showed high stability in saline, human serum or when challenged with DTPA, transferrin and varying metals (Fe3+, Cu2+, Zn2+). Conversely, the stability in human blood was low, and varying metabolites were detected and identified by ESI-MS. Conclusion: All three precursors are available in high yields suitable for routine production. NODAGA-AMBA showed the most favoured features when labelled with 68-gallium, but a further comparison in vivo should be performed in order to confirm the superior features found in vitro.

AB - The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and breast cancer, but the influence of different chelators, which differ in terms of radiochemical reactivity and stability, have not been explored so far. In order to find the best suitable chelator for labelling of AMBA, we synthesized AMBA analogues linked to the most commonly used chelators DOTA, NOTA and NODAGA and compared their reactivity and stability after labelling with 68-Gallium. Methods: For the synthesis of DO3A-, NO2A- and NODAGA-AMBA, a solid-phase synthesis approach was used. The influence of concentration, pH and temperature on the radiolabelling was analysed. The in vitro stability of all complexes in saline, human serum, human whole blood and against transchelation and transmetallation was analysed. Results: The peptides were synthesised in high yield and purity. Purity and identity of products and impurities were confirmed using UHPLC coupled to ESI-MS. Radiolabelling of these peptides was optimal at elevated temperature, although room temperature labelling was reported previously for NOTA and NODAGA chelators. The highest reactivity was observed for NODAGA-AMBA. On preparation of NO2A-AMBA, the formation of a by-product was detected with HPLC. More detailed analysis revealed the formation of an isomer with the same mass to charge ratio which led to the conclusion that a coordination isomer was formed. All complexes showed high stability in saline, human serum or when challenged with DTPA, transferrin and varying metals (Fe3+, Cu2+, Zn2+). Conversely, the stability in human blood was low, and varying metabolites were detected and identified by ESI-MS. Conclusion: All three precursors are available in high yields suitable for routine production. NODAGA-AMBA showed the most favoured features when labelled with 68-gallium, but a further comparison in vivo should be performed in order to confirm the superior features found in vitro.

KW - Ga-labelling

KW - Ga-NODAGA-AMBA

KW - AMBA-chelators

KW - Bombesin analogues

KW - Gallium radionuclides

UR - http://www.scopus.com/inward/record.url?scp=84888361759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888361759&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2013.08.010

DO - 10.1016/j.nucmedbio.2013.08.010

M3 - Article

C2 - 24183610

AN - SCOPUS:84888361759

VL - 41

SP - 24

EP - 35

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 1

ER -