Targeted radionuclide therapy using a Wnt-targeted replicating adenovirus encoding the Na/I symporter

Area of Science:

• Oncolytic virotherapy
• Molecular imaging
• Cancer gene therapy

Background:

• The sodium-iodide symporter (hNIS) facilitates iodine uptake in cells.
• hNIS holds potential as a reporter gene for tracking viral delivery and as a therapeutic agent for radioiodine therapy.
• Combining imaging and therapeutic functions of hNIS in oncolytic adenoviruses is a novel strategy for cancer treatment.

Purpose of the Study:

• To develop and evaluate an oncolytic adenovirus (AdIP2) encoding hNIS for colorectal cancer.
• To assess the imaging capabilities of hNIS for monitoring viral biodistribution.
• To investigate the therapeutic efficacy of (131)I-mediated radiotherapy using hNIS-expressing adenoviruses.

Main Methods:

• Generation of AdIP2, an adenovirus with selective replication in colorectal cancer cells.
• In vitro and in vivo verification of AdIP2 selectivity.
• In vivo tumor imaging using (99m)TcO(4)(-) and single-photon emission computed tomography/CT.
• Immunohistochemical confirmation of viral spread and hNIS expression.
• Administration of (131)I for metabolic radiotherapy.

Main Results:

• AdIP2 demonstrated selective replication and hNIS expression in target colorectal cancer cells, confirmed both in vitro and in vivo.
• Imaging and immunohistochemistry revealed limited viral spread, with peak hNIS expression at 48 hours post-injection.
• A single dose of (131)I administered at peak hNIS expression significantly reduced tumor size compared to controls.

Conclusions:

• This study demonstrates the successful combination of imaging and therapeutic applications of hNIS within an oncolytic adenovirus platform.
• The developed AdIP2 shows promise for targeted colorectal cancer therapy, integrating diagnostic imaging with radiotherapy.
• This represents a novel strategy for enhancing the efficacy of oncolytic virotherapy in preclinical cancer models.