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@ARTICLE{Knopf:186589,
author = {P. Knopf and D. Stowbur and S. H. L. Hoffmann and M. F.
Fransen and J. Schwenck and B. Pichler$^*$ and M. Kneilling},
title = {{P}reclinical {I}dentification {O}f {T}umor-{D}raining
{L}ymph {N}odes {U}sing a {M}ultimodal {N}on-invasive {I}n
vivo {I}maging {A}pproach.},
journal = {Molecular imaging and biology},
volume = {25},
number = {3},
issn = {1536-1632},
address = {Cham},
publisher = {Springer Nature Switzerland},
reportid = {DKFZ-2023-00025},
pages = {606-618},
year = {2023},
abstract = {Resection of the tumor-draining lymph -node (TDLN)
represents a standard method to identify metastasis for
several malignancies. Interestingly, recent preclinical
studies indicate that TDLN resection diminishes the efficacy
of immune checkpoint inhibitor-based cancer immunotherapies.
Thus, accurate preclinical identification of TDLNs is
pivotal to uncovering the underlying immunological
mechanisms. Therefore, we validated preclinically, and
clinically available non-invasive in vivo imaging approaches
for precise TDLN identification.For visualization of the
lymphatic drainage into the TDLNs by non-invasive in vivo
optical imaging, we injected the optical imaging contrast
agents Patent Blue V (582.7 g mol-1) and IRDye® 800CW
polyethylene glycol (PEG; 25,000-60,000 g mol-1),
subcutaneously (s.c.) in close proximity to MC38
adenocarcinomas at the right flank of experimental mice. For
determination of the lymphatic drainage and the glucose
metabolism in TDLNs by non-invasive in vivo PET/magnetic
resonance imaging (PET/MRI), we injected the positron
emission tomography (PET) tracer
(2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) [181.1 g mol-1])
in a similar manner. For ex vivo cross-correlation, we
isolated TDLNs and contralateral nontumor-draining lymph
nodes (NTDLNs) and performed optical imaging,
biodistribution, and autoradiography analysis.The clinically
well-established Patent Blue V was superior for
intraoperative macroscopic identification of the TDLNs
compared with IRDye® 800CW PEG but was not sensitive enough
for non-invasive in vivo detection by optical imaging. Ex
vivo Patent Blue V biodistribution analysis clearly
identified the right accessory axillary and the proper
axillary lymph node (LN) as TDLNs, whereas ex vivo IRDye®
800CW PEG completely failed. In contrast, functional
non-invasive in vivo 18F-FDG PET/MRI identified a
significantly elevated uptake exclusively within the
ipsilateral accessory axillary TDLN of experimental mice and
was able to differentiate between the accessory axillary and
the proper LN. Ex vivo biodistribution and autoradiography
confirmed our in vivo 18F-FDG PET/MRI results.When taken
together, our results demonstrate the feasibility of
18F-FDG-PET/MRI as a valid method for non-invasive in vivo,
intraoperative, and ex vivo identification of the lymphatic
drainage and glucose metabolism within the TDLNs. In
addition, using Patent Blue V provides additive value for
the macroscopic localization of the lymphatic drainage both
visually and by ex vivo optical imaging analysis. Thus, both
methods are valuable, easy to implement, and cost-effective
for preclinical identification of the TDLN.},
keywords = {18F-FDG (Other) / Optical imaging (Other) / PET/MRI (Other)
/ Patent Blue V (Other) / Tumor-draining lymph nodes
(Other)},
cin = {TU01},
ddc = {570},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36600172},
doi = {10.1007/s11307-022-01797-z},
url = {https://inrepo02.dkfz.de/record/186589},
}