ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2006
Imaging chemically modified adenovirus for targeting tumors expressing integrin alphavbeta3 in living mice with mutant herpes simplex virus type 1 thymidine kinase PET reporter gene.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 54 citations in OpenAlex.
- Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion.Nucleic acids research · 2015Article
- Design of a functional cyclic HSV1-TK reporter and its application to PET imaging of apoptosis.Nature protocols · 2015Article
- Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.European journal of nuclear medicine and molecular imaging · 2015Article
- Peptide-based technologies to alter adenoviral vector tropism: ways and means for systemic treatment of cancer.Viruses · 2014Review
- The evolution of adenoviral vectors through genetic and chemical surface modifications.Viruses · 2014Review
- Beyond Gene Delivery: Strategies to Engineer the Surfaces of Viral Vectors.Biomedicines · 2013Review
- Impact of the arterial input function on microvascularization parameter measurements using dynamic contrast-enhanced ultrasonography.World journal of radiology · 2012Article
- Peptide targeting of adenoviral vectors to augment tumor gene transfer.Cancer gene therapy · 2012Article
- 111In-labeled cystine-knot peptides based on the Agouti-related protein for targeting tumor angiogenesis.Journal of biomedicine & biotechnology · 2012Article
- Specific biomarkers of receptors, pathways of inhibition and targeted therapies: pre-clinical developments.The British journal of radiology · 2011Review
- Macrocyclic chelator assembled RGD multimers for tumor targeting.Bioorganic & medicinal chemistry letters · 2011Article
- Retargeting adenoviral vectors to improve gene transfer into tumors.Cancer gene therapy · 2011Article
- Article
- PEGylated Adenoviruses: From Mice to Monkeys.Viruses · 2010Article
- Therapeutic opportunities of small interfering RNA.Fundamental & clinical pharmacology · 2009Review
- Titration of variant HSV1-tk gene expression to determine the sensitivity of 18F-FHBG PET imaging in a prostate tumor.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2009Article
- Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody.European journal of nuclear medicine and molecular imaging · 2007Article
- Are quantum dots ready for in vivo imaging in human subjects?Nanoscale research letters · 2007Article
- Targeted delivery of siRNA.Journal of biomedicine & biotechnology · 2006Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThe aim of this study was to change adenovirus tropism by chemical modification of the fiber knobs with PEGylated RGD peptide for targeting integrin alpha(v)beta(3) that is uniquely or highly expressed in tumor cells and neovasculature of tumors of various origins.
methodsThe first generation Ad (Ad) vector, which expresses the herpes simplex virus type 1 mutant thymidine kinase (HSV1-sr39tk) gene under the control of cytomegalovirus (CMV) promoter was conjugated with poly(ethylene glycol) (PEG) or RGD-PEG. The transduction efficiency of Ads (Adtk, PEG-Adtk, and RGD-PEG-Adtk) into different types of cells (293T, MCF7, MDA-MB-435, and U87MG) was analyzed and quantified by thymidine kinase (TK) assay using 8-(3)H-penciclovir (8-(3)H-PCV) as substrate. The in vivo infectivity of the Ad vectors after intravenous administration into integrin alpha(v)beta(3)-positive U87MG and MDA-MB-435 tumor-bearing athymic nude mice was measured by both noninvasive microPET using 9-[4-(18)F-fluoro-3-(hydroxymethyl)butyl]guanine ((18)F-FHBG) as a reporter probe and ex vivo TK assay of the tumor and tissue homogenates.
resultsPEGylation completely abrogated coxsackievirus and adenovirus receptor (CAR)-knob interaction and the infectivity of PEG-Adtk is significantly lower than that of unmodified Adtk in CAR-positive cells. RGD-PEG-modified virus (RGD-PEG-Adtk) had significantly higher infectivity than PEG-Adtk and the extent of increase is related to both CAR and integrin alpha(v)beta(3) expression levels. (18)F-FHBG had minimal nonspecific uptake in the liver and tumors that are void of sr39tk. Mice preinjected intravenously with unmodified Adtk resulted in high hepatic uptake and moderate tumor accumulation of the tracer. In contrast, RGD-PEG-Adtk administration resulted in significantly lower liver uptake without compromising the tumor accumulation of (18)F-FHBG. Expression of TK in the liver and tumor homogenates corroborated with the magnitude of (18)F-FHBG uptake quantified by noninvasive microPET. Analysis of liver and tumor tissue integrin level confirmed that RGD-integrin interaction is responsible for the enhanced tumor infectivity of RGD-PEG-Adtk.
conclusionThe results of this study suggest that RGD-PEG conjugation is an effective way to modify Ad vector tropism for improved systemic gene delivery. Noninvasive PET and (18)F-FHBG are able to monitor in vivo transfectivity of both Adtk and RGD-PEG-Adtk vectors in the liver and tumors after intravenous injection.
Indexed as
Identifiers
16391197PMC4154793W2118592127What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.