Leveraging Open Science Drug Development for PET: Preliminary Neuroimaging of ¹¹C-Labeled ALK2 Inhibitors.

ABSTRACT: Mutations in the gene encoding activin receptor-like kinase 2 (ALK2) are implicated in the pathophysiology of a pediatric brainstem cancer, diffuse intrinsic pontine glioma (DIPG). Inhibitors of ALK2 that cross the blood-brain barrier have been proposed as a method of treatment for DIPG. As part of an open science approach to radiopharmaceutical and drug discovery, we developed ¹¹C-labeled radiotracers from potent and selective lead ALK2 inhibitors to investigate their brain permeability through positron emission tomography (PET) neuroimaging. Four radiotracers were synthesized by ¹¹C-methylation and assessed by dynamic PET imaging in healthy Sprague-Dawley rats. One of the compounds, [ ¹¹ C]M4K2127, showed high initial brain uptake (SU

SUBMITTER: Murrell E 

PROVIDER: S-EPMC8155239 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature