PET can be used to visualize ultrasound- and nanobubble-mediated gene transfer (sonoporation) and may be applied to clinical protocols of gene therapy, according to a study presented at the World Molecular Imaging Conference (WMIC) earlier this month in Kyoto, Japan.
The development of nonviral gene delivery systems is essential in gene therapy, and the use of a minimally invasive imaging methodology can provide important clinical endpoints, according to Yukiko Watanabe, PhD candidate, from the graduate school of biomedical engineering at Tohoku University in Miyagi, Japan.
In the study, two reporter vectors, [luciferase and human Na/I symporter (NIS)] were delivered into the skeletal (tibialis anterior) muscles of normal mice (BALB/c) by using nanobubbles and ultrasound as a non-viral gene delivery method. Watanabe and colleagues evaluated whether human NIS gene transfer by the ultrasound-nanobubble method could be detected by the practical semiconductor animal PET with a CdTe detector or fine structure imaging PET (fine-PET) in mice by using iodine-124 as radiotracer.
At the peak of gene transfer, PET imaging of human NIS expression was performed by Watanabe and colleagues using the fine-PET, following injection of iodine-124. The imaging data were confirmed using RT-PCR amplification, biodistribution, and blocking study.
The researchers evaluated imaging potential of the two methodologies-luciferase gene expression and PET imaging in two mice models of human pathology with one showing vascular disease, and the other showing muscular dystrophy.
The kinetics of luciferase gene expression was analyzed by using in vivo bioluminescence imaging system. Watanabe and colleagues observed peak luciferase gene activity four days after transfection.
PET imaging of the human NIS gene, biodistribution, the blocking study, and autoradiography were carried out four days after transfection, which indicated that human NIS expression was restricted to the transfection site (tibialis anterior muscle). Similar localized PET imaging and iodine-124 accumulation were successfully obtained in the disease-model mice.
The human NIS gene was successfully delivered into the skeletal muscle of healthy and disease-model mice by the ultrasound-nanobubble method, and gene expression was visualized with PET. The combination of ultrasound-nanobubble gene transfer and PET imaging may be applied to gene therapy clinical protocols, concluded Watanabe and colleagues.