Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate.
J Med Chem
; 67(6): 4793-4803, 2024 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-38450559
ABSTRACT
Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or ß--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
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Ácido Edético
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Radioisótopos de Gálio
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Compostos Heterocíclicos com 1 Anel
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article