In vivo assessment of tumor targeting potential of 68Ga-labelled randomly methylated beta-cyclodextrin (RAMEB) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) using positron emission tomography

Judit P Szabó; Katalin Csige; Ibolya Kálmán-Szabó; Viktória Arató; Gábor Opposits; István Jószai; István Kertész; Zita Képes; Gábor Méhes; Ferenc Fenyvesi; István Hajdu; György Trencsényi

doi:10.1016/j.ijpharm.2022.122462

In vivo assessment of tumor targeting potential of ⁶⁸Ga-labelled randomly methylated beta-cyclodextrin (RAMEB) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) using positron emission tomography

Int J Pharm. 2023 Jan 5:630:122462. doi: 10.1016/j.ijpharm.2022.122462. Epub 2022 Nov 30.

Authors

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; Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032, Debrecen, Hungary.
² Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Doctoral School of Pharmaceutical Sciences, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
³ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032, Debrecen, Hungary.
⁴ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁵ Department of Pathology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁶ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
⁷ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary; Doctoral School of Clinical Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032, Debrecen, Hungary; Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei St. 98, H-4032, Debrecen, Hungary. Electronic address: trencsenyi.gyorgy@med.unideb.hu.

PMID: 36462739
DOI: 10.1016/j.ijpharm.2022.122462

Abstract

Cyclodextrin derivates (CyDs) can form complexes with cyclooxygenase-2 induced tumor promoting prostaglandin E2 (PGE2). Based on our previous observations, ⁶⁸Ga-labelled CyDs may represent promising radiopharmaceuticals in the positron emission tomography (PET) diagnostics of PGE2 positive tumors. We aimed at evaluating the tumor-targeting potential of ⁶⁸Ga-NODAGA conjugated randomly methylated beta-cyclodextrin (⁶⁸Ga-NODAGA-RAMEB) and 2-hydroxypropyl-β-cyclodextrin (⁶⁸Ga-NODAGA-HPβCD) using in vivo PET imaging with experimental tumor models. Tumor radiopharmaceutical uptake was assessed applying PET and gamma counter in vivo and ex vivo respectively, following the administration of ¹⁸FDG, ⁶⁸Ga-NODAGA-RAMEB or ⁶⁸Ga-NODAGA-HPβCD via the lateral tail vein to the subsequent tumor-bearing animals: HT1080, A20, PancTu-1, BxPC3, B16-F10, Ne/De and He/De. All investigated tumors were identifiable with both ⁶⁸Ga-labelled CyDs; however, in vivo results, in correlation with the ex vivo data, revealed that the PGE2 positive BxPC3, A20, Ne/De and He/De tumors presented the highest accumulation. In case of HT1080, A20, B16-F10 tumors significant differences were encountered between the accumulations of both ⁶⁸Ga-labelled radiopharmaceuticals of the same tumor. Subcutaneously and the orthotopically transplanted Ne/De tumors differed significantly (p ≤ 0.01) regarding tracer uptake. ⁶⁸Ga-labelled CyDs may open a novel field in the PET diagnostics of PGE2 positive primary tumors and metastases.

Keywords: (68)Ga; Cyclodextrin; Positron Emission Tomography; prostaglandin E2.

MeSH terms

2-Hydroxypropyl-beta-cyclodextrin
Acetates
Animals
Cell Line, Tumor
Dinoprostone
Gallium Radioisotopes*
Heterocyclic Compounds, 1-Ring
Positron-Emission Tomography / methods
Radiopharmaceuticals
beta-Cyclodextrins*

Substances

1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
2-Hydroxypropyl-beta-cyclodextrin
Acetates
beta-Cyclodextrins
Dinoprostone
Gallium Radioisotopes
Heterocyclic Compounds, 1-Ring
Radiopharmaceuticals