Citation Details

Journal Article

HCT-116-luc2, HCT116-luc2, IVIS, Animals; Antibodies, Monoclonal/administration & dosage/*immunology; Antigens, CD45/metabolism; Cell Line, Tumor; Cell Transformation, Neoplastic/pathology; Disease Models, Animal; Flow Cytometry; Fluorescent Dyes/*metabolism; Humans; Imaging, Three-Dimensional/*methods; Injections, Intravenous; Leukemia/*diagnosis/*pathology; Leukemia, Myeloid, Acute/pathology; Longevity; Luminescent Measurements; Mice; Mice, SCID; Reproducibility of Results; Spectroscopy, Near-Infrared/*methods

BACKGROUND: The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI) to determine when to start treatments with novel antitumor agents. METHODS: Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc) were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. RESULTS: The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI) and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. CONCLUSIONS: A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented.

Journal Article

HCT-116-luc2, IVIS, Bioware, HCT116-luc2, Administration, Oral; Animals; Bacteria/*genetics; Cell Line, Tumor; Female; Genes, Reporter/genetics; Genetic Engineering; Glioblastoma/*microbiology/pathology/radiography; Humans; Imaging, Three-Dimensional; Luminescent Measurements/*methods; Lung Neoplasms/*microbiology/pathology/radiography; Mice; Molecular Imaging/*methods; X-Ray Microtomography

The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (muCT) for interpretation.In this study, the non-pathogenic commensal bacteria E. coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (i.v.) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and muCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations.

Journal Article

Immunology;Volocity; Xen14

N/A

Journal Article

In vivo imaging; AngioSPARK

N/A

Journal Article

In vivo imaging; atherosclerosis; bioluminescence imaging; fluorescence imaging; myocardial infarction; stroke; ProSense

Pathophysiological processes in the vascular system are the major cause of mortality and disease. Atherosclerosis, an inflammatory process in arterial walls, can lead to formation of plaques, whose rupture can lead to thrombus formation, obstruction of vessels (thrombosis), reduction of the blood flow (ischemia), cell death in the tissue fed by the occluded vessel, and depending on the affected vessel, to myocardial infarction or stroke. Imaging techniques enabling visualization of the biological processes involved in this scenario are therefore highly desirable. In recent years, a number of reporter agents and reporter systems have been developed to visualize these processes using different imaging modalities including nuclear imaging techniques, such as positron emission tomography or single photon emission computed tomography, magnetic resonance imaging, and ultrasound. This article comprises a brief overview of optical imaging techniques, such as fluorescence imaging and bioluminescence imaging for the visualization of vascular pathophysiology.