| As oncolytic vectors for cancer therapy come to clinical trials, noninvasive monitoring of vector biodistribution will be necessary. Oncolytic vaccinia viruses (rVV) preferentially target, infect and replicate in tumours. The goal of this research was to develop non-invasive strategies of monitoring rVV in vivo. Upon subcutaneous murine colon cancer tumour formation and subsequent systemic administration of rVV in athymic mice, we acquired whole-body mouse images by nuclear medicine or optical (fluorescence) techniques. Fluorescence imaging revealed the earliest time-point of enhanced green fluorescent protein (EGFP) detection and persistence in tumours of mice infected with an EGFP-expressing rVV. In vitro binding studies confirmed specific radioligand binding of 111In-pentetreotide and [123I]IBF to vaccinia virus-mediated expression of human somatostatin receptor subtype 2 (hSSTR2) and the dopamine D2 receptor (DRD2) on tumour cells, respectively. In vivo studies examined biodistribution and specificity of 111In-Pentetreotide and [123I]IBF in athymic mice after systemic delivery of vvDD-hSSTR2 and vvDD-EGFP-DRD2, respectively. Optical and nuclear imaging of rVV expressing EGFP, hSSTR2, and DRD2 provides a non-invasive assessment of vector biodistribution and persistence, and potentially will be able to image tumour responses. |
