In vivo imaging of oligonucleotides with positron emission tomography

Tavitian, Bertrand; Terrazzino, Salvatore; Kühnast, Bertrand; S, Marzabal; Stettler, Olivier; Dollé, Frédéric; Deverre,; Jobert, Antoinette; Hinnen, Françoise; Bendriem, B.; Crouzel, C.; L, Di Giamberardino

doi:10.1038/nm0498-467

Cited by 197 publications

(124 citation statements)

References 13 publications

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“…Hence, LY2181308 clearly accumulated in tumor tissue over time (17). This is consistent with studies in animals, where the distribution and stability of the second-generation ASOs was evaluated (9,27). Other FHD studies evaluating inhibitors of the IAP family have not reported similar PD changes in solid tumor tissue after dosing with ASOs.…”

Section: Discussionsupporting

confidence: 87%

Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study

Talbot¹,

Ranson²,

Davies³

et al. 2010

Clin Cancer Res

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Purpose: Enhanced tumor cell survival through expression of inhibitors of apoptosis (IAP) is a hallmark of cancer. Survivin, an IAP absent from most normal tissues, is overexpressed in many malignancies and associated with a poorer prognosis. We report the first-in-human dose study of LY2181308, a secondgeneration antisense oligonucleotide (ASO) directed against survivin mRNA.Patients and Methods: A dose-escalation study evaluating the safety, pharmacokinetics, and pharmacodynamics of LY2181308 administered intravenously for 3 hours as a loading dose on 3 consecutive days and followed by weekly maintenance doses. Patients were eligible after signing informed consent, had exhausted approved anticancer therapies and agreed to undergo pre-and posttreatment tumor biopsies to evaluate reduction of survivin protein and gene expression.Results: A total of 40 patients were treated with LY2181308 at doses of 100 to 1,000 mg. Twenty-six patients were evaluated at the recommended phase 2 dose of 750 mg, at which level serial tumor sampling and

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Section: Discussionsupporting

confidence: 87%

Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study

Talbot¹,

Ranson²,

Davies³

et al. 2010

Clin Cancer Res

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“…Aptamers are single-stranded RNA or DNA oligonucleotides with unique intramolecular conformations that hold distinct binding properties to various targets, including small molecules, proteins, and even entire organisms (3)(4)(5). As a small, polyanionic and nonimmunogenic type of probe, aptamers may exhibit faster tissue penetration and uptake, shorter residence in blood and nontarget organs, and higher ratio of target accumulation, thus affording great potential for in vivo cancer imaging (6,7).…”

mentioning

confidence: 99%

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Shi

He²,

Wang³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

279

225

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Aptamers have emerged as promising molecular probes for in vivo cancer imaging, but the reported "always-on" aptamer probes remain problematic because of high background and limited contrast. To address this problem, we designed an activatable aptamer probe (AAP) targeting membrane proteins of living cancer cells and achieved contrast-enhanced cancer visualization inside mice. The AAP displayed a quenched fluorescence in its free state and underwent a conformational alteration upon binding to target cancer cells with an activated fluorescence. As proof of concept, in vitro analysis and in vivo imaging of CCRF-CEM cancer cells were performed by using the specific aptamer, sgc8, as a demonstration. It was confirmed that the AAP could be specifically activated by target cancer cells with a dramatic fluorescence enhancement and exhibit improved sensitivity for CCRF-CEM cell analysis with the cell number of 118 detected in 200 μl binding buffer. In vivo studies demonstrated that activated fluorescence signals were obviously achieved in the CCRF-CEM tumor sites in mice. Compared to always-on aptamer probes, the AAP could substantially minimize the background signal originating from nontarget tissues, thus resulting in significantly enhanced image contrast and shortened diagnosis time to 15 min. Furthermore, because of the specific affinity of sgc8 to target cancer cells, the AAP also showed desirable specificity in differentiating CCRF-CEM tumors from Ramos tumors and nontumor areas. The design concept can be widely adapted to other cancer cell-specific aptamer probes for in vivo molecular imaging of cancer.switchable aptamer probe | in vivo imaging | activatable fluorescent molecular imaging | cancer detection | cell surface protein

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“…Due to its positron-emission properties, fluorine-18 (radioactive isotope of fluorine) is widely used for oligonucleotide labeling for in vivo PET (Positron Emission Tomography) imaging. Dollé et al [96][97][98][99][100]. have developed an original method for labeling oligonucleotides with 18 F in different positions.…”

Section: Application Of Fluorinated Oligonucleotide Analoguesmentioning

confidence: 99%

Nucleic Acid Based Fluorinated Derivatives: New Tools for Biomedical Applications

et al. 2012

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In vivo imaging of oligonucleotides with positron emission tomography

Cited by 197 publications

References 13 publications

Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study

Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Nucleic Acid Based Fluorinated Derivatives: New Tools for Biomedical Applications

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