non-invasive-vivo-fluorescence-optical-imaging-inflammatory-mmp

Non-invasive <em>In Vivo</em> Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent

This paper describes a non-invasive method for imaging matrix metalloproteinases (MMP)-activity by an activatable fluorescent probe, via in vivo ...

Eberhard Karls University of Tübingen

Combined PET and MR imaging (PET/MR imaging) has progressed tremendously in recent years. The focus of current research has shifted from technologic challenges to the application of this new multimodal imaging technology in the areas of oncology, cardiology, neurology, and infectious diseases. This article reviews studies in preclinical and clinical translation. The common theme of these initial results is the complementary nature of combined PET/MR imaging that often provides additional insights into biologic systems that were not clearly feasible with just one modality alone. However, in vivo findings require ex vivo validation. Combined PET/MR imaging also triggers a multitude of new developments in image analysis that are aimed at merging and using multimodal information that ranges from better tumor characterization to analysis of metabolic brain networks. The combination of connectomics information that maps brain networks derived from multiparametric MR data with metabolic information from PET can even lead to the formation of a new research field that we would call cometomics that would map functional and metabolic brain networks. These new methodologic developments also call for more multidisciplinarity in the field of molecular imaging, in which close interaction and training among clinicians and a variety of scientists is needed.

Preclinical and Translational PET/MR Imaging.

In vivo visualization of prostate-specific membrane antigen in glioblastoma.

The aim of this study was to determine whether the severity of contact hypersensitivity reactions (CHSRs) can be observed by noninvasive in vivo optical imaging of matrix metalloproteinase (MMP) activity and whether this is an appropriate tool for monitoring an antiinflammatory effect. Acute and chronic CHSRs were elicited by application of a 1% trinitrochlorobenzene (TNCB) solution for up to five times on the right ear of TNCB-sensitized mice. N-Acetylcysteine (NAC)-treated and sham-treated mice were monitored by measuring ear swelling and optical imaging of MMP activity. In addition, we performed hematoxylin-eosin staining and CD31 immunohistochemistry for histopathologic analysis of the antiinflammatory effects of NAC. The ear thickness and the MMP activity increased in line with the increasing severity of the CHSR. MMP activity was enhanced 2.5- to 2.7-fold during acute CHSR and 3.1- to 4.1-fold during chronic CHSR. NAC suppressed ear swelling and MMP signal intensity in mice with acute and chronic CHSR. During chronic CHSR, the vessel density was significantly reduced in ear sections derived from NAC-treated compared to sham-treated mice. In vivo optical imaging of MMP activity measures acute and chronic CHSR and is useful to monitor antiinflammatory effects.

In vivo optical imaging of matrix metalloproteinase activity detects acute and chronic contact hypersensitivity reactions and enables monitoring of the antiinflammatory effects of N-acetylcysteine.

Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. ©2016 AACR.

Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study.

Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using (11)C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand (68)Ga-PSMA-11 with (11)C-choline in patients with primary and recurrent prostate cancer.

Article	Year
Preclinical and Translational PET/MR Imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine\| PubMed ID: 24833493	2014
In vivo visualization of prostate-specific membrane antigen in glioblastoma. European journal of nuclear medicine and molecular imaging\| PubMed ID: 25293865	2015
In vivo optical imaging of matrix metalloproteinase activity detects acute and chronic contact hypersensitivity reactions and enables monitoring of the antiinflammatory effects of N-acetylcy... Molecular imaging\| PubMed ID: 25430819	2014
Decoding Intratumoral Heterogeneity of Breast Cancer by Multiparametric In Vivo Imaging: A Translational Study. Cancer research\| PubMed ID: 27466286	2016
Comparison of (68)Ga-labelled PSMA-11 and (11)C-choline in the detection of prostate cancer metastases by PET/CT. European journal of nuclear medicine and molecular imaging\| PubMed ID: 27557844	2017

Johannes Schwenck

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