High resolution of U‐SPECT/CT system helps perform kinetic analyses of viral spread in vivo

Sep 12 2013

High resolution of U‐SPECT/CT enables kinetic analysis of viral spread in vivo for the first time

The ability to visualize and analyze the spread of viral infections in primary and metastatic tumors is an essential component in characterizing the therapeutic efficacy of oncolytic viruses. This should ideally be performed in vivo but had so far, not been feasible due to the insufficient resolution provided by existing preclinical imaging systems. The high resolution of the recently installed U‐SPECT/CT system at The Mayo Clinic allowed Dr. Roberto Cattaneo and his group for the first time, to perform longitudinal kinetic and quantitative analyses of viral spread in primary and metastatic tumors. The results have been published in the August edition of the journal Molecular Therapy from the Nature Publishing Group.

A basic SPECT/CT system that the group owned previously was used initially for this study but radioisotope uptake in small structures could not be quantified at that time due to insufficient resolution. The study was resumed with the U‐SPECT/CT from MILabs. It was able to provide the image quality and sensitivity that enabled the researchers to align infectious centers in 3D, following their evolution and dynamics, for over 2 weeks post‐therapy. The researchers could visualize the relative intensity of infection within individual foci using its wide dynamic range. It was conclusively shown that data obtained in vivo correlated well with data obtained after tumor harvest using methods such as autoradiography and immunohistochemistry using Hoechst dye.

Dr. Cattaneo and his group were also able to accurately quantify isotope uptake in the metastatic tumors as well as the thyroid in terms of injected dose or uptake concentrated per cubic centimeter. This is also a new benchmark as this quantification can be extremely challenging due to the close proximity of the thyroid to the NIS‐expressing salivary glands. The accuracy and reproducibility of the results of quantification of isotope uptake per cubic cm for primary and metastatic tumors highlighted by the fact that they closely correlate to harvested tumors measured per gram of tissue. The group also characterized the viral entry pathway supporting productive infection and oncolysis through their imaging studies, establishing the immune‐cell specific protein SLAM as the dominant oncolytic receptor.

This body of research has opened up the possibility to investigate oncolysis in not only mantle cell lymphoma but any cancer type derived from tissues in which viruses have evolved to replicate at high levels such as breast, lung and ovarian carcinomas.