Expression of the NIS transgene in MV-NIS infected tumors allowed for single photon emission computed tomography and positron emission tomography-computed tomography imaging of virus infected tumors in vivo.
The recombinant baculovirus supports a promising strategy of NIS-based raidoiodide therapy combined with K5-based antiangiogenic therapy by targeting both the tumor and its supporting vessels.
We therefore investigated the potential of a novel oncolytic vaccinia virus GLV1h-153 engineered to express the hNIS gene for identifying positive surgical margins after tumor resection via positron emission tomography (PET).
An oncolytic measles virus with an additional transcriptional unit encoding the sodium iodide symporter (NIS), as a reporter for viral infection, was mixed with a 1:10 dilution of Omnipaque 300 (GE Healthcare, Milwaukee, WI, USA) contrast agent and injected directly into tumors.
These results demonstrate efficient liver detargeting and tumor retargeting of adenoviral vectors after coating with synthetic dendrimers, thereby representing a promising innovative strategy for systemic NIS gene therapy.
These data demonstrate successful stromal targeting of NIS in HCC tumors by selective recruitment of NIS-expressing MSCs and by use of the RANTES/CCL5 promoter.
In vivo experiments demonstrated that 3 days after intratumoral (i.t.) injection of Ad5-E1/AFP-E3/NIS HuH7 xenograft tumors accumulated approximately 25% ID g(-1) (percentage of the injected dose per gram tumor tissue) (123)I as shown by (123)I gamma camera imaging.A single i.t. injection of Ad5-E1/AFP-E3/NIS (virotherapy) resulted in a significant reduction of tumor growth and prolonged survival, as compared with injection of saline.
Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression.
Cotransfer of thyroid-specific transcription factor (TTF)-1 and Pax-8 gene to tumor cells, resulting in the re-expression of iodide metabolism-associated proteins, such as sodium iodide symporter (NIS), thyroglobulin (Tg), thyroperoxidase (TPO), offers the possibility of radioiodine therapy to non-iodide-concentrating tumor because the expression of iodide metabolism-associated proteins in thyroid are mediated by the thyroid transcription factor TTF-1 and Pax-8.
Radiovirotherapy of xenograft LNCaP tumors with Ad5/3PB-ADP-hNIS showed the most significant survival extension versus control tumors (p=0.001), but the benefit of radiovirotherapy was not statistically significant compared with virotherapy alone in this model.
MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS), has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone.
By day 14, the tumor was visible with a significant reduction in radionuclide accumulation in nontarget tissue observed. hNIS gene expression was detected in the intestines, heart, lungs, and tumors at early time points but later depleted in nontarget tissues and persisted at the tumor site.
Clonogenic assays demonstrated that Ad-SUR-NIS-infected cancer cells were selectively killed by exposure to (131)I. Ad-SUR-NIS-infected tumors show significant radioiodine accumulation (13.3 ± 2.85% ID per g at 2 h post-injection), and the effective half-life was 3.1 h. Moreover, infection with Ad-SUR-NIS in combination with (131)I suppressed tumor growth.
Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.
As intracellular iodine is released rapidly, increased expression of sodium/iodide symporter (NIS) is required for effective radioiodine treatment of tumor.
These results clearly demonstrate that biodegradable nanoparticles based on OEI-grafted oligoamines show increased efficiency for systemic NIS gene transfer in an HCC model with similar tumor selectivity as compared with LPEI-PEG-GE11, and therefore represent a promising strategy for NIS-mediated radioiodine therapy of HCC.
We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery.
After adenovirus-mediated NIS gene transfer in HepG2 xenografts administration of a therapeutic dose of (131)I or (188)Re (55.5 MBq) resulted in a significant delay in tumor growth and improved survival without a significant difference between (188)Re and (131)I.
In the orthotopic tumor model, the presence of NIS conferred almost 4 times the boron concentration in rat tumors transfected with human virus compared with contralateral normal brain not transfected.