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@ARTICLE{Malviya:289026,
author = {G. Malviya and T. R. M. Lannagan and E. Johnson and A.
Mackintosh and R. Bielik and A. Peters and D. Soloviev and
G. Brown and R.-F. Jackstadt$^*$ and C. Nixon and K. Gilroy
and A. Campbell and O. J. Sansom and D. Y. Lewis},
title = {{N}oninvasive {S}tratification of {C}olon {C}ancer by
{M}ultiplex {PET} {I}maging.},
journal = {Clinical cancer research},
volume = {30},
number = {8},
issn = {1078-0432},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2024-00558},
pages = {1518-1529},
year = {2024},
note = {DKFZ-ZMBH Alliance / 2024 Apr 15;30(8):1518-1529},
abstract = {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.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).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.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.},
cin = {A013},
ddc = {610},
cid = {I:(DE-He78)A013-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38493804},
doi = {10.1158/1078-0432.CCR-23-1063},
url = {https://inrepo02.dkfz.de/record/289026},
}