Dataset Information

Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin.

ABSTRACT: Purpose: mTOR regulates many normal physiological processes and when hyperactive can drive numerous cancers and human diseases. However, it is very challenging to detect and quantify mTOR signaling noninvasively in clinically relevant animal models of disease or man. We hypothesized that a nuclear imaging tool measuring intracellular mTOR activity could address this unmet need.Experimental Design: Although the biochemical activity of mTOR is not directly amenable to nuclear imaging probe development, we show that the transferrin receptor can be used to indirectly measure intracellular changes in mTOR activity.Results: After verifying that the uptake of radiolabeled transferrin (the soluble ligand of the transferrin receptor) is stimulated by active mTORC1 in vitro, we showed that 89Zr-labeled transferrin (Tf) can measure mTORC1 signaling dynamics in normal and cancerous mouse tissues with PET. Finally, we show that 89Zr-Tf can detect the upregulation of mTORC1 by tumor cells to escape the antitumor effects of a standard-of-care antiandrogen, which is to our knowledge the first example of applying PET to interrogate the biology of treatment resistant cancer.Conclusions: In summary, we have developed the first quantitative assay to provide a comprehensive measurement of mTOR signaling dynamics in vivo, in specific normal tissues, and during tumor development in genetically engineered animal models using a nuclear imaging tool that is readily translatable to man. Clin Cancer Res; 23(12); 3045-52. ©2016 AACR.

SUBMITTER: Truillet C

PROVIDER: S-EPMC5474159 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin.

Truillet Charles C Cunningham John T JT Parker Matthew F L MFL Huynh Loc T LT Conn Crystal S CS Ruggero Davide D Lewis Jason S JS Evans Michael J MJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20161222 12

Purpose: mTOR regulates many normal physiological processes and when hyperactive can drive numerous cancers and human diseases. However, it is very challenging to detect and quantify mTOR signaling noninvasively in clinically relevant animal models of disease or man. We hypothesized that a nuclear imaging tool measuring intracellular mTOR activity could address this unmet need.Experimental Design: Although the biochemical activity of mTOR is not directly amenable to nuclear imaging ...[more]

PMID: 28007777

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Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin.

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Noninvasive Measurement of mTORC1 Signaling with <sup>89</sup>Zr-Transferrin.

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