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Synthesis, radiolabeling, and pre-clinical evaluation of [44Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer.

Background

Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [44Sc][Sc-(AAZTA)]− and two derivatives, i.e., [44Sc][Sc (CNAAZTA-BSA)] and [44Sc][Sc (CNAAZTA-cRGDfK)].

Results

B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [44Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes.

Conclusions

This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgments

We thank Lorenzo Tei for supporting synthesis activity.

Funding

The research was totally supported by Bracco Imaging SpA.

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Authors and Affiliations

  1. Bracco Research Centre, Bracco Imaging SpA, Via Ribes 5, 10010, Colleretto Giacosa (TO), Italy

    S. Ghiani & Z. Baranyai

  2. Dipartimento di Biotecnologie Molecolari e Scienze per la salute, Centro di Imaging Molecolare, Università degli Studi di Torino, Via Nizza 52, 10126, Torino, Italy

    I. Hawala & R. Stefania

  3. Scanomed Ltd., Nagyerdei krt. 98, Debrecen, 4032, Hungary

    D. Szikra, G. Trencsényi, G. Nagy & A. Vágner

  4. Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary

    D. Szikra & G. Trencsényi

  5. Bracco Research USA Inc., 259 Prospect Plains Rd., Bldg. H, Monroe Township, NJ, 08831, USA

    S. Pandey

  6. Bracco SpA, Via Caduti di Marcinelle, 13, 20134, Milan, Italy

    A. Maiocchi

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  1. S. Ghiani
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Correspondence to S. Ghiani.

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The authors declare that they have no competing interests.

Ethics approval and informed consent

All procedures performed in studies involving animals were in accordance with the ethical standards of the Hungarian Laws and regulations of the European Union (Permission numbers: animal house: XXVIII-KÁT/2015, ethical license for the study: 19/2017/DE MÁB). Approval for this study was granted by the Scientific Ethics Council of Animal Experiments.

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Ghiani, S., Hawala, I., Szikra, D. et al. Synthesis, radiolabeling, and pre-clinical evaluation of [44Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer. Eur J Nucl Med Mol Imaging 48, 2351–2362 (2021). https://doi.org/10.1007/s00259-020-05130-0

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  • DOI: https://doi.org/10.1007/s00259-020-05130-0

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