Synthesis and preliminary PET imaging of ¹¹C and ¹⁸F isotopologues of the ROS1/ALK inhibitor lorlatinib.

ABSTRACT: Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumour lesions of lung cancer patients, as penetration of the blood-brain barrier is important for optimal therapeutic outcomes. Here we prepare both ¹¹C- and ¹⁸F-isotopologues of lorlatinib to determine the biodistribution and whole-body dosimetry assessments by positron emission tomography (PET). Non-traditional radiolabelling strategies are employed to enable an automated multistep

SUBMITTER: Collier TL 

PROVIDER: S-EPMC5472746 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature