Citation Details

Journal Article

VivoTag, IVIS, Vivotag, Animals; Antibodies, Monoclonal/*diagnostic use/immunology/pharmacokinetics; Antigens, Neoplasm/*metabolism; Blotting, Western; Breast/immunology/metabolism/pathology; Breast Neoplasms/*diagnosis/immunology/metabolism; Carbonic Anhydrases/*metabolism; Carcinoma, Ductal, Breast/*diagnosis/immunology/metabolism; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/immunology/metabolism; *Diagnostic Imaging; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Humans; Luciferases/metabolism; Luminescent Measurements; Lymphatic Metastasis; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Tissue Array Analysis; Tissue Distribution; Tumor Cells, Cultured; Tumor Markers, Biological/genetics/metabolism

PURPOSE: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. EXPERIMENTAL DESIGN: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. RESULTS: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. CONCLUSION: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities.

Journal Article

In vivo imaging; AngioSense

Extract:

With the advent of tissue regeneration and gene therapy for heart disease, evaluation of coronary circulation and cardiac function in vivo, especially in a disease model, is extremely important. Conventional methods such as microcomputed tomography, high-resolution magnetic resonance angiography, and high-resolution ultrasound have become invaluable tools in cardiovascular research. However, the disadvantages and limitations of these approaches sometimes preclude researchers from conducting important and specific studies on coronary circulation and cardiac function. Therefore, we developed and applied a novel real-time, in vivo fluorescent optical imaging system for use in the mouse cardiovascular system. We report the use of this system for repeatedly assessing coronary circulation, cardiovascular structure, and cardiac function in live mice...

Journal Article

Cardiovascular disease; in vivo imaging; atherosclerosis; magnetic resonance imaging; thrombosis; myocardial infarction; diagnostic imaging; molecular imaging

No abstract available.

Journal Article

In vivo imaging; inflammation; leukocytes; rejection; transplantation; fluorescence molecular tomography; FMT; Prosense

Background: Clinical detection of transplant rejection by repeated endomyocardial biopsy requires catheterization and entails risks. Recently developed molecular and cellular imaging techniques that visualize macrophage host responses could provide a noninvasive alternative. Yet, which macrophage functions may provide useful markers for detecting parenchymal rejection remains uncertain.

Methods and Results: We transplanted isografts from B6 mice and allografts from Balb/c mice heterotopically into B6 recipients. In this allograft across major histocompatability barriers, the transplanted heart undergoes predictable progressive rejection, leading to graft failure after 1 week. During rejection, crucial macrophage functions, including phagocytosis and release of proteases, render these abundant innate immune cells attractive imaging targets. Two or 6 days after transplantation, we injected either a fluorescent protease sensor or a magnetofluorescent phagocytosis marker. Histological and flow cytometric analyses established that macrophages function as the major cellular signal source. In vivo, we obtained a 3-dimensional functional map of macrophages showing higher phagocytic uptake of magnetofluorescent nanoparticles during rejection using magnetic resonance imaging and higher protease activity in allografts than in isografts using tomographic fluorescence. We further assessed the sensitivity of imaging to detect the degree of rejection. In vivo imaging of macrophage response correlated closely with gradually increasing allograft rejection and attenuated rejection in recipients with a genetically impaired immune response resulting from a deficiency in recombinase-1 (RAG-1-/-).

Conclusions: Molecular imaging reporters of either phagocytosis or protease activity can detect cardiac allograft rejection noninvasively, promise to enhance the search for novel tolerance-inducing strategies, and have translational potential.

Journal Article

in vivo imaging; atherosclerosis; cathepsin K; fluorescence; imaging; inflammation; AngioSense

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