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Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.


ABSTRACT:

Purpose

The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression-based subtyping remain unknown.

Experimental design

In this study, we conducted 126 PET scans using four different metabolic PET tracers, [18F]fluorodeoxy-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), and [11C]acetate ([11C]ACE), using a spectrum of five preclinical colon cancer models with varying genetics (BMT, AKPN, AK, AKPT, KPN), at three sites (subcutaneous, orthograft, autochthonous) and at two tumor stages (primary vs. metastatic).

Results

The results demonstrate that imaging signatures are influenced by genotype, tumor environment, and stage. PET imaging signatures exhibited significant heterogeneity, with each cancer model displaying distinct radiotracer profiles. Oncogenic Kras and Apc loss showed the most distinctive imaging features, with [18F]FLT and [18F]FET being particularly effective, respectively. The tissue environment notably impacted [18F]FDG uptake, and in a metastatic model, [18F]FET demonstrated higher uptake.

Conclusions

By examining factors contributing to PET-imaging phenotype, this study establishes the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. It lays the foundation for further exploration of PET-based subtyping in human cancer, thereby facilitating noninvasive molecular diagnosis.

SUBMITTER: Malviya G 

PROVIDER: S-EPMC11016897 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.

Malviya Gaurav G   Lannagan Tamsin R M TRM   Johnson Emma E   Mackintosh Agata A   Bielik Robert R   Peters Adam A   Soloviev Dmitry D   Brown Gavin G   Jackstadt Rene R   Nixon Colin C   Gilroy Kathryn K   Campbell Andrew A   Sansom Owen J OJ   Lewis David Y DY  

Clinical cancer research : an official journal of the American Association for Cancer Research 20240401 8


<h4>Purpose</h4>The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and  ...[more]

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