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[⁶⁸Ga]NS₃-RGD and [⁶⁸Ga] Oxo-DO3A-RGD for imaging α(v)β₃ integrin expression: synthesis, evaluation, and comparison.

Abstract：

INTRODUCTION:⁶⁸Ga-labeled RGD peptides in combination with PET allow non-invasive determination of α(v)β₃ integrin expression which is highly increased during tumor-induced angiogenesis. The aim of this study was to synthesize and evaluate two RGD peptides containing alternative chelating systems, namely [⁶⁸Ga]NS₃-RGD-RGD and [⁶⁸Ga]Oxo-DO3A-RGD and to compare their in vitro and in vivo properties with [⁶⁸Ga]DOTA- and [⁶⁸Ga]NODAGA-RGD. METHODS:Syntheses of both radiotracers followed standard SPPS protocols. For in vitro characterization distribution coefficients, protein binding abilities, serum stabilities, and α(v)β₃ integrin binding affinities were determined. For in vitro tests as well as for the biodistribution assay α(v)β₃ positive human melanoma M21 and α(v)β₃ negative M21-L cells were used. RESULTS:⁶⁸Ga-labeling of NS₃-RGD resulted in good radiochemical purity, whereas HPLC analysis showed two peaks with a ratio of 1:6 for [⁶⁸Ga]Oxo-DO3A-RGD. Distribution coefficients were -3.4 for [⁶⁸Ga]Oxo-DO3A-RGD and -2.9 for [⁶⁸Ga]NS₃-RGD. Both radiotracers were stable in PBS solution at 37°C for 2 h but lack stability in human serum. Protein binding was approximately 40% of the total activity for [⁶⁸Ga]NS₃-RGD and 70% for [⁶⁸Ga]Oxo-DO3A-RGD, respectively, resulting in high blood pool activities. Biodistribution assays confirmed these findings and showed an additional high uptake in liver and kidneys, especially for [⁶⁸Ga]NS₃-RGD. Furthermore, [⁶⁸Ga]Oxo-DO3A-RGD showed nearly the same activity concentrations in α(v)β₃ positive and α(v)β₃ negative tumors. CONCLUSIONS:[⁶⁸Ga]Oxo-DO3A-RGD and [⁶⁸Ga]NS₃-RGD have inferior characteristics compared to already existing ⁶⁸Ga-labeled RGD peptides and thus, both are not suited to image α(v)β₃ integrin expression. Of all our tested RGD peptides, [⁶⁸Ga]NODAGA-RGD still possesses the most favorable imaging properties. Moreover this study shows that the use of appropriate chelators to achieve good targeting properties of ⁶⁸Ga-labeled biomolecules and careful in vitro and in vivo evaluation including comparative studies of different strategies are essential components in designing an effective imaging agent for PET.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Knetsch PA,Petrik M,Rangger C,Seidel G,Pietzsch HJ,Virgolini I,Decristoforo C,Haubner R

doi

10.1016/j.nucmedbio.2012.09.006

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

65-72

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(12)00251-X

journal_volume

pub_type

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[⁶⁸Ga]NS₃-RGD and [⁶⁸Ga] Oxo-DO3A-RGD for imaging α(v)β₃ integrin expression: synthesis, evaluation, and comparison.