In vivo comparison of N-11CH3 vs O-11CH3 radiolabeled microtubule targeted PET ligands.
Bioorg Med Chem Lett
; 30(2): 126785, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31753695
ABSTRACT
Altered dynamics of microtubules (MT) are implicated in the pathophysiology of a number of brain diseases. Therefore, radiolabeled MT targeted ligands that can penetrate the blood brain barrier (BBB) may offer a direct and sensitive approach for diagnosis, and assessing the clinical potential of MT targeted therapeutics using PET imaging. We recently reported two BBB penetrating radioligands, [11C]MPC-6827 and [11C]HD-800 as specific PET ligands for imaging MTs in brain. The major metabolic pathway of the above molecules is anticipated to be via the initial labeling site, O-methyl, compared to the N-methyl group. Herein, we report the radiosynthesis of N-11CH3-MPC-6827 and N-11CH3-HD-800 and a comparison of their in vivo binding with the corresponding O-11CH3 analogues using microPET imaging and biodistribution methods. Both O-11CH3 and N-11CH3 labeled MT tracers exhibit high specific binding and brain. The N-11CH3 labeled PET ligands demonstrated similar in vivo binding characteristics compared with the corresponding O-11CH3 labeled tracers, [11C]MPC-6827 and [11C]HD-800 respectively.
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MEDLINE
Assunto principal:
Compostos Radiofarmacêuticos
/
Microtúbulos
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article