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Journal Article

ProSense; schistosomiasis; platyhelminth; parasite; fluorescence molecular tomography; FMT; in vivo imaging

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Journal Article

FMT; OsteoSense; ProSense bone mineralization; bone turnover markers; molecular imaging; bisphosphonates; in vivo imaging

Abstract: FRFP binds to mineral at osteoblastic, osteoclastic, and quiescent surfaces, with accumulation likely modulated by vascular delivery. In vivo visualization and quantification of binding can be accomplished noninvasively in animal models through optical tomographic imaging.

Introduction: The development of near-infrared optical markers as reporters of bone metabolism will be useful for early diagnosis of disease. Bisphosphonates bind differentially to osteoblastic and osteoclastic surfaces depending on choice of side-chain and dose, and fluorescently tagged bisphosphonates provide a convenient way to visualize these sites. This study examines the ability of a fluorescently labeled pamidronate imaging probe to bind to regions of bone formation and resorption in vivo.

Materials and Methods: In vitro binding of a far-red fluorescent pamidronate (FRFP) to mineral was assessed using intact and demineralized dentine slices. In vivo, FRFP binding was studied in three models: developing neonatal mouse, bone healing after injury, and metastasis-induced osteolysis and fracture. 3D fluorescence molecular tomographic (FMT) imaging was used to visualize signal deep within the body.

Results: FRFP binding to bone depends on the quantity of mineral present and can be liberated from the bone during decalcification. In vivo, FRFP binds to surfaces of actively forming bone, as assessed by alkaline phosphatase staining, surfaces undergoing active resorption, as noted by scalloped bone border and presence of osteoclasts, and to quiescent surfaces not involved in formation or resorption. Binding is likely modulated by vascular delivery of the imaging agent to the exposed mineral surface and total quantity of surface exposed.FMT imaging is capable of visualizing regions of bone formation because of a large volume of labeled surface, but like radiolabeled bone scans, cannot discriminate pure osteolysis caused by metastasis.

Conclusions: FRFP may function as a local biomarker of bisphosphonate deposition to assess interplay between drug and cellular environment or may be combined with other imaging agents or fluorescent cells for the noninvasive assessment of local bone metabolism in vivo.

Journal Article

IntegriSense, Animals; Cell Line, Tumor; Fiber Optic Technology/*methods; Fluorescent Dyes/*administration & dosage/*diagnostic use; Humans; Injections, Intralesional; Lung Neoplasms/*pathology; Microscopy, Fluorescence/*methods; Molecular Imaging/*methods; Rabbits; Surgery, Computer-Assisted/*methods; Tomography, X-Ray Computed/methods

PURPOSE: To show the feasibility of computed tomography (CT) image-guided fiberoptic confocal fluorescence molecular imaging in a rabbit lung tumor model. MATERIALS AND METHODS: Eight lung tumor models were created by injection of a VX2 cell suspension. The fluorescent imaging agent IntegriSense 680 was given to the animals 3.5-4 hours before the procedure. CT images were obtained and transferred to the minimally invasive multimodality image-guided (MIMIG) system as a guidance map. A real-time electromagnetically tracked needle was inserted under the visual guidance of the MIMIG system. A second CT image was obtained to confirm the location of the needle tip. Next, fiberoptic fluorescence imaging was acquired along the needle track. Finally, tumor samples were obtained for histopathologic confirmation. RESULTS: All cases were performed during breath-hold. Tumor size was 12.5 mm +/- 1.6; the distance from the chest wall was 2.1 mm +/- 0.5. The needle tip reached the tumor in all cases with an accuracy of 3.3 mm +/- 1.6. Only one skin entry point was necessary, and no needle adjustments were required. No pneumothorax was observed. At least two-fold alpha(v)beta(3) integrin image contrast was detected in the tumor compared with normal lung tissue. Tumor samples were confirmed to have viable VX2 cells and contrast uptake. CONCLUSIONS: The MIMIG system enables effective in situ fluorescence molecular imaging in a needle biopsy lung procedure. In situ alpha(v)beta(3) integrin molecular imaging allows molecular characterization of lung tumors at multiple regions and can be used to guide biopsy procedures.

Journal Article

in vivo imaging; fluorescence molecular tomography

We report the synthesis and in vivo characterization of an 18F modified trimodal nanoparticle (18F-CLIO). This particle consists of cross-linked dextran held together in core-shell formation by a superparamagnetic iron oxide core and functionalized with the radionuclide 18F in high yield via “click” chemistry. The particle can be detected with positron emission tomography, fluorescence molecular tomography, and magnetic resonance imaging. The presence of 18F dramatically lowers the detection threshold of the nanoparticles, while the facile conjugation chemistry provides a simple platform for rapid and efficient nanoparticle labeling.

Journal Article

A549-luc-C8; Animals; Bioware; Cell Line, Tumor; Colonic Neoplasms; Fluorouracil; HT-29-luc-D6 cells; Humans; Image Interpretation, Computer-Assisted; Longitudinal Studies; Luciferases; Luminescent Measurements; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, SCID; Mitomycin; Models, Biological; Neoplasm Transplantation; PC-3M-luc; Prostatic Neoplasms

Bioluminescent imaging (BLI) permits sensitive in vivo detection and quantification of cells specifically engineered to emit visible light. Three stable human tumor cell lines engineered to express luciferase were assessed for their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted subcutaneously into SCID-beige mice and were monitored for tumor growth and response to 5-FU and mitomycin C treatments. Progressive tumor development and inhibition/regression following drug treatment were observed and quantified in vivo using BLI. Imaging data correlated to standard external caliper measurements of tumor volume, but bioluminescent data permitted earlier detection of tumor growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung cancer cells were injected intravenously and lung metastases were monitored in vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a temporal assessment of in vivo lung tumor growth. This longitudinal study design permitted an accurate, real-time evaluation of tumor burden in the same animals over time. End-point bioluminescence measured in vivo correlated to total lung weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT-29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases to lung and lymph nodes in SCID-beige mice. Both primary tumors and micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung lobes and lymph nodes confirmed the in vivo signals and indicated a slightly higher frequency of metastasis in some mice. Levels of bioluminescence from in vivo and ex vivo images corresponded to the frequency and size of metastatic lesions in lungs and lymph nodes as subsequently confirmed by histology. In summary, BLI provided rapid, non-invasive monitoring of tumor growth and regression in animals. Its application to traditional oncology animal models offers quantitative and sensitive analysis of tumor growth and metastasis. The ability to temporally assess tumor development and responses to drug therapies in vivo also improves upon current standard animal models that are based on single end point data.