68Ga-NODAGA-RGD is a suitable substitute for 18F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process

Karolin Pohle; Johannes Notni; Johanna Bussemer; Horst Kessler; Markus Schwaiger; Ambros J. Beer

doi:10.1016/j.nucmedbio.2012.02.006

⁶⁸Ga-NODAGA-RGD is a suitable substitute for ¹⁸F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process

Karolin Pohle
, Johannes Notni
, Johanna Bussemer
, Horst Kessler
, Markus Schwaiger
, Ambros J. Beer

TUM Emeriti of Excellence

Technical University of Munich
Kind AbdulAziz University

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Introduction: ¹⁸F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with ⁶⁸Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for ¹⁸F-Galacto-cyclo(RGDfK). Methods: ⁶⁸Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO ₂ based ⁶⁸Ga-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both ¹⁸F-Galacto-cyclo(RGDfK) and ⁶⁸Ga-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC ₅₀ was determined in a displacement assay on M21 cells against ¹²⁵I-echistatin. Results: ⁶⁸Ga-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500GBq/μmol) within 15 min. IC ₅₀ values are similar for both substances. Tracer uptake was similar in ανβ3 positive tumors (1.45%±0.11% ID/g and 1.35%±0.53% ID/g for ⁶⁸Ga-NODAGA-RGD and ¹⁸F-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where ¹⁸F-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of ⁶⁸Ga-NODAGA-cyclo(RGDyK) (logP=-4.0 vs. -3.2 for ¹⁸F-Galacto-RGD). Only intact tracer was detected 30min p.i. in organs and tumor; however, minor amounts of metabolites were found in the urine (6% of total urine activity). Conclusion: ⁶⁸Ga-labeling of NODAGA-RGD can be performed rapidly and efficiently within 15min in a GMP compliant process. Similar preclinical results were obtained in comparison with ¹⁸F-Galacto-RGD. Therefore, ⁶⁸Ga-NODAGA-cyclo(RGDyK) is a suitable replacement for ¹⁸F-Galacto-cyclo(RGDfK).

Original language	English
Pages (from-to)	777-784
Number of pages	8
Journal	Nuclear Medicine and Biology
Volume	39
Issue number	6
DOIs	https://doi.org/10.1016/j.nucmedbio.2012.02.006
State	Published - Aug 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Ga-NODAGA-RGD
Gallium-68
Positron emission tomography
RGD peptides
ανβ3 integrin

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10.1016/j.nucmedbio.2012.02.006

Cite this

@article{2f30a81e53d9455b87441c926546dd6e,

title = "68Ga-NODAGA-RGD is a suitable substitute for 18F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process",

abstract = "Introduction: 18F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with 68Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for 18F-Galacto-cyclo(RGDfK). Methods: 68Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO 2 based 68Ga-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both 18F-Galacto-cyclo(RGDfK) and 68Ga-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC 50 was determined in a displacement assay on M21 cells against 125I-echistatin. Results: 68Ga-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500GBq/μmol) within 15 min. IC 50 values are similar for both substances. Tracer uptake was similar in ανβ3 positive tumors (1.45\%±0.11\% ID/g and 1.35\%±0.53\% ID/g for 68Ga-NODAGA-RGD and 18F-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where 18F-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of 68Ga-NODAGA-cyclo(RGDyK) (logP=-4.0 vs. -3.2 for 18F-Galacto-RGD). Only intact tracer was detected 30min p.i. in organs and tumor; however, minor amounts of metabolites were found in the urine (6\% of total urine activity). Conclusion: 68Ga-labeling of NODAGA-RGD can be performed rapidly and efficiently within 15min in a GMP compliant process. Similar preclinical results were obtained in comparison with 18F-Galacto-RGD. Therefore, 68Ga-NODAGA-cyclo(RGDyK) is a suitable replacement for 18F-Galacto-cyclo(RGDfK).",

keywords = "Ga-NODAGA-RGD, Gallium-68, Positron emission tomography, RGD peptides, ανβ3 integrin",

author = "Karolin Pohle and Johannes Notni and Johanna Bussemer and Horst Kessler and Markus Schwaiger and Beer, \{Ambros J.\}",

note = "Funding Information: This work was carried out within the MOBITUM project “Improved ligands for quantitative monitoring of integrin expression” (MOBITEC/MOBITUM 01EZ0826) at TU Munich. Financial support of the German Research Foundation (SFB 824 project Z1) is gratefully acknowledged. We thank Gjermund Hendriksen and Michael Herz for 18 F-Galacto-RGD synthesis, Christina Lesti and Rosel Oos for cell culture \& animal handling, Sybille Reder, Markus Mittelh{\"a}user and Marco Lehmann for performing animal PET/CT experiments.",

year = "2012",

month = aug,

doi = "10.1016/j.nucmedbio.2012.02.006",

language = "English",

volume = "39",

pages = "777--784",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - 68Ga-NODAGA-RGD is a suitable substitute for 18F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process

AU - Pohle, Karolin

AU - Notni, Johannes

AU - Bussemer, Johanna

AU - Kessler, Horst

AU - Schwaiger, Markus

AU - Beer, Ambros J.

N1 - Funding Information: This work was carried out within the MOBITUM project “Improved ligands for quantitative monitoring of integrin expression” (MOBITEC/MOBITUM 01EZ0826) at TU Munich. Financial support of the German Research Foundation (SFB 824 project Z1) is gratefully acknowledged. We thank Gjermund Hendriksen and Michael Herz for 18 F-Galacto-RGD synthesis, Christina Lesti and Rosel Oos for cell culture & animal handling, Sybille Reder, Markus Mittelhäuser and Marco Lehmann for performing animal PET/CT experiments.

PY - 2012/8

Y1 - 2012/8

N2 - Introduction: 18F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with 68Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for 18F-Galacto-cyclo(RGDfK). Methods: 68Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO 2 based 68Ga-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both 18F-Galacto-cyclo(RGDfK) and 68Ga-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC 50 was determined in a displacement assay on M21 cells against 125I-echistatin. Results: 68Ga-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500GBq/μmol) within 15 min. IC 50 values are similar for both substances. Tracer uptake was similar in ανβ3 positive tumors (1.45%±0.11% ID/g and 1.35%±0.53% ID/g for 68Ga-NODAGA-RGD and 18F-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where 18F-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of 68Ga-NODAGA-cyclo(RGDyK) (logP=-4.0 vs. -3.2 for 18F-Galacto-RGD). Only intact tracer was detected 30min p.i. in organs and tumor; however, minor amounts of metabolites were found in the urine (6% of total urine activity). Conclusion: 68Ga-labeling of NODAGA-RGD can be performed rapidly and efficiently within 15min in a GMP compliant process. Similar preclinical results were obtained in comparison with 18F-Galacto-RGD. Therefore, 68Ga-NODAGA-cyclo(RGDyK) is a suitable replacement for 18F-Galacto-cyclo(RGDfK).

AB - Introduction: 18F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with 68Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for 18F-Galacto-cyclo(RGDfK). Methods: 68Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO 2 based 68Ga-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both 18F-Galacto-cyclo(RGDfK) and 68Ga-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC 50 was determined in a displacement assay on M21 cells against 125I-echistatin. Results: 68Ga-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500GBq/μmol) within 15 min. IC 50 values are similar for both substances. Tracer uptake was similar in ανβ3 positive tumors (1.45%±0.11% ID/g and 1.35%±0.53% ID/g for 68Ga-NODAGA-RGD and 18F-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where 18F-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of 68Ga-NODAGA-cyclo(RGDyK) (logP=-4.0 vs. -3.2 for 18F-Galacto-RGD). Only intact tracer was detected 30min p.i. in organs and tumor; however, minor amounts of metabolites were found in the urine (6% of total urine activity). Conclusion: 68Ga-labeling of NODAGA-RGD can be performed rapidly and efficiently within 15min in a GMP compliant process. Similar preclinical results were obtained in comparison with 18F-Galacto-RGD. Therefore, 68Ga-NODAGA-cyclo(RGDyK) is a suitable replacement for 18F-Galacto-cyclo(RGDfK).

KW - Ga-NODAGA-RGD

KW - Gallium-68

KW - Positron emission tomography

KW - RGD peptides

KW - ανβ3 integrin

UR - https://www.scopus.com/pages/publications/84863990736

U2 - 10.1016/j.nucmedbio.2012.02.006

DO - 10.1016/j.nucmedbio.2012.02.006

M3 - Article

C2 - 22444238

AN - SCOPUS:84863990736

SN - 0969-8051

VL - 39

SP - 777

EP - 784

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 6

ER -