Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging

Author:

Malviya Gaurav12ORCID,Lannagan Tamsin R.M.1ORCID,Johnson Emma1ORCID,Mackintosh Agata1ORCID,Bielik Robert1ORCID,Peters Adam1ORCID,Soloviev Dmitry1ORCID,Brown Gavin1ORCID,Jackstadt Rene34ORCID,Nixon Colin1ORCID,Gilroy Kathryn1ORCID,Campbell Andrew1ORCID,Sansom Owen J.12ORCID,Lewis David Y.12ORCID

Affiliation:

1. 1Cancer Research UK Scotland Institute, Garscube Estate, Glasgow, United Kingdom.

2. 2School of Cancer Sciences, University of Glasgow; Glasgow, United Kingdom.

3. 3Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.

4. 4Cancer Progression and Metastasis Group, German Cancer Research Center (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany. German Cancer Consortium (DKTK), Germany.

Abstract

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.

Funder

Beatson Institute for Cancer Research

Beatson Cancer Charity

Publisher

American Association for Cancer Research (AACR)

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