Molecular imaging of oncolytic viral therapy

Abstract

Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

“…Generally, real-time tracking of virus evolution can optimize treatment by providing useful information regarding the viral dose and administration schedule, as well as the elimination of the need for multiple and repeated tissue biopsies. Moreover, the ability of molecular imaging to improve vector design and clinical protocols facilitates the use of personalized medicine in the treatment of cancer [22,[24][25][26].…”

“…charge-coupled device (CCD) cameras) are the most common imaging modalities applied in non-nuclear medicine. These external imaging devices use light as a nonradioactive probe and are predominantly restricted to preclinical assays [25,27]. Nevertheless, nuclear molecular imaging tools such as SPECT, positron emission tomography (PET) scanner, and gamma camera modalities can potentially be used in clinical trials and due to their ability to recognize and localize the gamma-ray emitted by a radioactive tracer decay, they can provide more reliable information about virotherapy outcomes.…”

“…Of note, serial monitoring of infection, prediction of the primary site of tumors and metastases, as well as evaluation of antitumor efficacy are possible using the genetically engineered viruses that express a reporter gene, which can be imaged by molecular imaging modalities [22,25,28]. In this manner, the accumulation of tracer molecules at the site of transgene expression and recognition of their emitted signals by external imaging devices is used to follow the viral evolution in tissues of interest.…”

“…In this manner, the accumulation of tracer molecules at the site of transgene expression and recognition of their emitted signals by external imaging devices is used to follow the viral evolution in tissues of interest. It is worth noting that these targeting moieties or signaling agents introduced as imaging molecular probes should not be immunogenic, or otherwise interfere with the function of subject cells [25,27,29].…”

Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging

“…Genes encoding the intracellular transport, binding, or uptake of radioactive tracers in place of normal proteins have emerged as an innovative strategy for non-invasive visualization of tumor growth in animal models [5–7]. Reporter gene imaging is based on vector-mediated overexpression of a transgene that is not normally expressed in the host cells [8,9].…”