A new molecular imaging method can monitor the success of gene therapy in all areas of the brain that may allow physicians to effectively tackle brain conditions such as Parkinson’s disease, Alzheimer’s and multiple sclerosis, a new study suggests.
The researchers said that although reporter gene systems have been a key tool in molecular imaging for a number of years, they have not allowed monitoring of all areas of the brain.
“It is challenging to find a reporter gene and imaging agent that can be used in all areas of the brain with a high signal-to-background ratio,” said Thomas Haywood from the Stanford University, in California.
“18F-DASA-23 is a novel radiotracer or reporter probe, that is capable of crossing the blood-brain barrier and targeting the pyruvate kinase M2 protein in the central nervous system with minimal endogenous expression in the brain.”
“This allows us to monitor reporter gene expression and ultimately therapeutic gene expression for gene therapy in all regions of the brain,” Haywood said.
The researchers mentioned that radiotracer has recently undergone first-in-human trials for the early detection of therapeutic response in glioblastoma — most aggressive cancer that begins within the brain.
In the study, presented at the SNMMI 2018 Annual Meeting, after validating the utility of pyruvate kinase M2 (PKM2) as a PET reporter gene, mice were infected with a virus containing the gene, then imaged with the 18F-DASA-23 radiotracer over a period of two months to observe the increase in PKM2 expression over time.
The results, confirmed by 18F-DASA-23 uptake studies and mRNA analysis, showed a good correlation between PKM2 and the radiotracer.
Further analysis showed an increase in PKM2 expression in infected mice when compared to controls.
These encouraging data suggest PKM2 has the potential to be further developed into a PET reporter gene system for the imaging of gene therapy in the central nervous system, the researchers said.