Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response

Merrill, Joseph R, Inguscio, Alessandra, Chung, Taemoon, Demestichas, Breanna, Garcia, Libia A, Habel, Jill, Lewis, David Y, Janowitz, Tobias, Lyons, Scott K (August 2023) Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response. Cell Stress, 7 (8). pp. 59-68. ISSN 2523-0204

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Abstract

Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders > cancer diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes diseases & disorders > cancer > drugs and therapies > Immunotherapy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > luciferase organism description > animal > mammal organism description > animal > mammal > rodent > mouse diseases & disorders > cancer > cancer types > pancreatic cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent diseases & disorders > cancer > cancer types
CSHL Authors:	Merrill, Joseph Demestichas, Breanna Garcia, Libia Habel, Jill Janowitz, Tobias Lyons, Scott Chung, Taemoon Inguscio, Alessandra
Communities:	CSHL labs > Janowitz lab CSHL labs > Lyons lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	14 August 2023
Date Deposited:	21 Sep 2023 15:03
Last Modified:	30 Apr 2024 18:42
PMCID:	PMC10468692
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40938

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