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 - http://www.scopus.com/inward/record.url?scp=84863990736&partnerID=8YFLogxK
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 -
