PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA

Ibolya Kálmán-Szabó; Judit P Szabó; Viktória Arató; Noémi Dénes; Gábor Opposits; István Jószai; István Kertész; Zita Képes; Anikó Fekete; Dezső Szikra; István Hajdu; György Trencsényi

doi:10.3390/ijms231710061

PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [⁶⁸Ga]Ga-NODAGA-AMBA and [⁴⁴Sc]Sc-NODAGA-AMBA

Int J Mol Sci. 2022 Sep 2;23(17):10061. doi: 10.3390/ijms231710061.

Authors

Ibolya Kálmán-Szabó^{1

2}, Judit P Szabó^{1

3}, Viktória Arató^{1

4}, Noémi Dénes¹, Gábor Opposits¹, István Jószai¹, István Kertész¹, Zita Képes¹, Anikó Fekete¹, Dezső Szikra¹, István Hajdu¹, György Trencsényi^{1

2

3}

Affiliations

¹ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
² Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
³ Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁴ Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.

Abstract

Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer (PCa). Since bombesin analogue aminobenzoic-acid (AMBA) binds to GRPR with high affinity, scandium-44 conjugated AMBA is a promising radiotracer in the PET diagnostics of GRPR positive tumors. Herein, the GRPR specificity of the newly synthetized [⁴⁴Sc]Sc-NODAGA-AMBA was investigated in vitro and in vivo applying PCa PC-3 xenograft. After the in-vitro assessment of receptor binding, PC-3 tumor-bearing mice were injected with [⁴⁴Sc]Sc/[⁶⁸Ga]Ga-NODAGA-AMBA (in blocking studies with bombesin) and in-vivo PET examinations were performed to determine the radiotracer uptake in standardized uptake values (SUV). ⁴⁴Sc/⁶⁸Ga-labelled NODAGA-AMBA was produced with high molar activity (approx. 20 GBq/µmoL) and excellent radiochemical purity. The in-vitro accumulation of [⁴⁴Sc]Sc-NODAGA-AMBA in PC-3 cells was approximately 25-fold higher than that of the control HaCaT cells. Relatively higher uptake was found in vitro, ex vivo, and in vivo in the same tumor with the ⁴⁴Sc-labelled probe compared to [⁶⁸Ga]Ga-NODAGA-AMBA. The GRPR specificity of [⁴⁴Sc]Sc-NODAGA-AMBA was confirmed by significantly (p ≤ 0.01) decreased %ID and SUV values in PC-3 tumors after bombesin pretreatment. The outstanding binding properties of the novel [⁴⁴Sc]Sc-NODAGA-AMBA to GRPR outlines its potential to be a valuable radiotracer in the imaging of GRPR-positive PCa.

Keywords: PC-3; [44Sc]Sc-NODAGA-AMBA; [68Ga]Ga-NODAGA-AMBA; bombesin (BBN); gastrin-releasing peptide receptor (GRPR); positron emission tomography (PET); prostate cancer (PCa).

MeSH terms

Acetates
Animals
Bombesin
Cell Line, Tumor
Gallium Radioisotopes
Heterocyclic Compounds, 1-Ring
Humans
Male
Mice
Positron-Emission Tomography / methods
Prostatic Neoplasms* / metabolism
Receptors, Bombesin* / metabolism

Substances

1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
Acetates
Gallium Radioisotopes
Heterocyclic Compounds, 1-Ring
Receptors, Bombesin
Bombesin

Grants and funding

The published work was supported by the EFOP-3.6.3-VEKOP-16-2017-00009 fund of European Union, by the NKFIH K119552 grant of the European Social Fund and National Research, Development and Innovation Office, and by the Thematic Excellence Programme (TKP2020-NKA-04) of the Ministry for Innovation and Technology in Hungary. This research was also supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (bo_328_21).