Modeling of [¹⁸F]-FHBG in tumor and normal tissues

Abstract

The development of new, non-invasive approaches for the treatment of tumors has led to the emergence of oncolytic virus therapy. Viruses have been engineered to preferentially target tumor cells. The efficiency and safety of this cancer treatment is dependent upon selective viral replication within cancer cells. In order for viral oncolysis to be successful in the clinical setting, the biodistribution of viral replication must be quantified. This study has used an enzyme-based positron emission tomography (PET) reporter system to trace the viral replication of herpes simplex virus (HSV)-l. [¹⁸F]FHBG was used as the substrate for the HSV-1 enzyme product - thymidine kinase (TK) - in order for PET imaging technique to identity sites of HSV-1 TK activity. The imaged mice were divided into three groups: a control group with no tumor growth and no viral injection, a control group with no tumor growth and viral injection, and an experimental group with both tumor growth and viral injection. The time-activity curves of [¹⁸F]FHBG accumulation in the heart, muscle, liver, kidneys, brain, and tumor were plotted for all three groups. A 3-Compartmental Model for the kinetics of [¹⁸F]FHBG accumulation within each of the organs was coded using MATLAB, with COMKAT implementation. The time-activity curves were fitted and the kinetic parameters k1, k2, and k3 were calculated. A unified model was additionally presented as a final verification of the calculated parameters. The 3-Comparmental Model developed in this study proved applicable and accurate, with significant applications to interpreting the behavior of specific organs and overall organ systems during viral oncolysis. The qualitative observations formed on the basis of quantitative results have important consequences on the safety and in vivo monitoring of oncolytic virus therapy.