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Radiosynthesis and preclinical evaluation of a 68Ga-labeled tetrahydroisoquinoline-based ligand for PET imaging of C-X-C chemokine receptor type 4 in an animal model of glioblastoma.
Suwattananuruk, Piyapan; Yaset, Sukanya; Chotipanich, Chanisa; Moldes-Anaya, Angel; Sundset, Rune; Berzaghi, Rodrigo; Figenschau, Stine; Claes, Sandra; Schols, Dominique; Rojsitthisak, Pornchai; Kranz, Mathias; Vajragupta, Opa.
Afiliación
  • Suwattananuruk P; Department of Food and Pharmaceutical Chemistry and Center of Excellence in Natural Products for Ageing and Chronic Diseases, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
  • Yaset S; Molecular Probes for Imaging Research Network, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
  • Chotipanich C; National Cyclotron and PET Centre, Chulabhorn Hospital, Bangkok, Thailand.
  • Moldes-Anaya A; National Cyclotron and PET Centre, Chulabhorn Hospital, Bangkok, Thailand.
  • Sundset R; PET Imaging Center, University Hospital of North Norway, Tromsø, Norway.
  • Berzaghi R; PET Imaging Center, University Hospital of North Norway, Tromsø, Norway.
  • Figenschau S; Department of Clinical Medicine, Nuclear Medicine and Radiation Biology Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
  • Claes S; Department of Clinical Medicine, Nuclear Medicine and Radiation Biology Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
  • Schols D; Department of Clinical Medicine, Nuclear Medicine and Radiation Biology Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
  • Rojsitthisak P; Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, KU Leuven, Louvain, Belgium.
  • Kranz M; Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, KU Leuven, Louvain, Belgium.
  • Vajragupta O; Department of Food and Pharmaceutical Chemistry and Center of Excellence in Natural Products for Ageing and Chronic Diseases, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
EJNMMI Radiopharm Chem ; 9(1): 61, 2024 Aug 20.
Article en En | MEDLINE | ID: mdl-39162901
ABSTRACT

BACKGROUND:

This study aimed to develop a novel positron emission tomography (PET) tracer, [68Ga]Ga-TD-01, for CXCR4 imaging. To achieve this goal, the molecular scaffold of TIQ15 was tuned by conjugation with the DOTA chelator to make it suitable for 68Ga radiolabeling.

METHODS:

A bifunctional chelator was prepared by conjugating the amine group of TIQ15 with p-NCS-Bz-DOTA, yielding TD-01, with a high yield (68.92%). TD-01 was then radiolabeled with 68Ga using 0.1 M ammonium acetate at 60 °C for 10 min. A 1-h dynamic small animal PET/MRI study of the labeled compound in GL261-luc2 tumor-bearing mice was performed, and brain tumor uptake was assessed. Blocking studies involved pre-administration of TIQ15 (10 mg/kg) 10 min before the PET procedure started.

RESULTS:

[68Ga]Ga-TD-01 exhibited a radiochemical yield (RCY) of 36.33 ± 1.50% (EOS), with a radiochemical purity > 99% and a molar activity of 55.79 ± 1.96 GBq/µmol (EOS). The radiotracer showed in vitro stability in PBS and human plasma for over 4 h. Biodistribution studies in healthy animals revealed favorable kinetics for subsequent PET pharmacokinetic modeling with low uptake in the brain and moderate uptake in lungs, intestines and spleen. Elimination could be assigned to a renal-hepatic pathway as showed by high uptake in kidneys, liver, and urinary bladder. Importantly, [68Ga]Ga-TD-01 uptake in glioblastoma (GBM)-bearing mice significantly decreased upon competition with TIQ15, with a baseline tumor-to-background ratios > 2.5 (20 min p.i.), indicating high specificity.

CONCLUSION:

The newly developed CXCR4 PET tracer, [68Ga]Ga-TD-01, exhibited a high binding inhibition for CXCR4, excellent in vitro stability, and favorable pharmacokinetics, suggesting that the compound is a promising candidate for full in vivo characterization of CXCR4 expression in GBM, with potential for further development as a tool in cancer diagnosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJNMMI Radiopharm Chem Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJNMMI Radiopharm Chem Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido