TrisOxine abiotic siderophores for technetium complexation: radiolabeling and biodistribution studies

• Published in: EJNMMI radiopharmacy and chemistry Vol. 8; no. 1; p. 32
• Main Authors: Leenhardt, Julien, Biguet Petit Jean, Alexandre, Raes, Florian, N’Guessan, Emilien, Debiossat, Marlène, André, Clémence, Bacot, Sandrine, Ahmadi, Mitra, de Leiris, Nicolas, Djaileb, Loïc, Ghezzi, Catherine, Brunet, Marie-Dominique, Broisat, Alexis, Perret, Pascale, du Moulinet d’Hardemare, Amaury
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 19.10.2023; Springer Nature B.V; London : Springer Open; SpringerOpen
• Subjects: 8-Hydroxyquinoline; Antibodies; Biodistribution; Chelates; Chelating agents; Chelation; Chemical Sciences; Complexation; Computed tomography; Emission analysis; Hydroxyquinoline; Imaging; In vivo methods and tests; Life Sciences; Ligands; Lipophilic; Medical imaging; Medicine; Medicine & Public Health; Molecular Medicine; Nuclear Chemistry; Nuclear Medicine; Octanol; Oxidation state; Peptides; Pharmacotherapy; Photon emission; Positron emission; Positron emission tomography; Radioactive tracers; Radiochemical purity; Radiochemistry; Radiolabelling; Radiology; Reducing agents; Research Article; Room temperature; Siderophores; Single photon emission computed tomography; Technetium; Technetium isotopes; Technetium-99m; Tin; Tomography; Siderophores; Oxidation state; Nano SPECT/CT imaging; Radiochemistry; Radiochemical purity; Chelates; Biodistribution; Technetium-99m
• DOI: 10.1186/s41181-023-00214-2
• ISSN: 2365-421X

Background Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O- TRENSOX and O- TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O- TRENOX and O -TRENSOX with 99m Tc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex’s charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [ 99m Tc]Tc- O- TRENOX and [ 99m Tc]Tc- O- TRENSOX were performed. Results The radiolabeling studies showed a rapid and efficient complexation of 99m Tc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [ 99m Tc]Tc- O- TRENOX complex with a radiochemical purity of more than 98% and the [ 99m Tc]Tc- O- TRENSOX complex with one above 97% at room temperature within 5 min. [ 99m Tc]Tc- O- TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [ 99m Tc]Tc- O- TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. Conclusions These encouraging results allow us to consider the O- TRENOX/ 99m Tc and O- TRENSOX/ 99m Tc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc.