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68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

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Abstract

Purpose

αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [18F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce 68Ga- and 111In-labelled derivatives and compare them with [18F]Galacto-RGD.

Methods

For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used.

Results

Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [68Ga]DOTA-RGD and only up to 1.4% for [111In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [68Ga]DOTA-RGD ([111In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [18F]Galacto-RGD: 1.6 ± 0.2%ID/g and 0.4 ± 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [68Ga]DOTA-RGD, tumour/blood ratios were higher for [111In]DOTA-RGD and [18F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [68Ga]DOTA-RGD is possible.

Conclusions

Our data indicate that [68Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [18F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [18F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator systems may overcome the disadvantages.

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Acknowledgement

Stefan Schwarz, Svetlana Sirakanyan and Sybille Reder are gratefully acknowledged for their excellent technical assistance. We thank Bettina Sarg, Division of Clinical Biochemistry, Medizinische Universität Innsbruck for carrying out the LC–MS analysis. David A. Cheresh, The Scripps Institute, La Jolla, CA was acknowledged for kindly providing the melanoma M21 and M21-L cells.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Medizinische Universität Innsbruck, Innsbruck, Austria

    Clemens Decristoforo, Ignacio Hernandez Gonzalez, Marco Rupprich, Irene Virgolini & Roland Haubner

  2. Department of Nuclear Medicine, Technische Universität München, Munich, Germany

    Janette Carlsen, Marc Huisman & Hans-Jürgen Wester

  3. Universitätsklinik für Nuklearmedizin, Medizinische Universität Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria

    Roland Haubner

Authors
  1. Clemens Decristoforo
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  2. Ignacio Hernandez Gonzalez
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  3. Janette Carlsen
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  4. Marco Rupprich
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  5. Marc Huisman
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  6. Irene Virgolini
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  7. Hans-Jürgen Wester
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  8. Roland Haubner
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Correspondence to Roland Haubner.

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Decristoforo, C., Hernandez Gonzalez, I., Carlsen, J. et al. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression. Eur J Nucl Med Mol Imaging 35, 1507–1515 (2008). https://doi.org/10.1007/s00259-008-0757-6

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  • DOI: https://doi.org/10.1007/s00259-008-0757-6

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