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Bioorg Chem ; 104: 104185, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32911200

RESUMO

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68Ga-based generator and radiotracers render independence from the on-site cyclotron. We report the development of 68Ga-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of 68Ga- DO3P-AME-DO3P was carried out in > 95% purity. The radiotracer displayed high stability and low binding affinity (<3%) to blood serum. High in vitro binding affinity were observed for synthetic hydroxyapatite, SAOS-2, osteoclast and osteoblast cells. In vivo pharmacokinetics revealed fast washout with biphasic release pattern. The deposition of radiotracer in osseous tissues was high (Bone/Muscle ratio:18), as studied from the biodistribution studies. In vivo PET/CT and biodistribution analyses revealed the ability of 68Ga-DO3P-AME-DO3P to target and accumulate in bone, thus displaying its potential as a PET bone imaging agent.


Assuntos
Acetamidas/química , Osso e Ossos/diagnóstico por imagem , Compostos Macrocíclicos/química , Compostos Organofosforados/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Acetamidas/sangue , Acetamidas/farmacocinética , Radioisótopos de Gálio , Humanos , Compostos Macrocíclicos/sangue , Compostos Macrocíclicos/farmacocinética , Estrutura Molecular , Compostos Organofosforados/sangue , Compostos Organofosforados/farmacocinética , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
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