Indicator dilution using a fluorescent indicator

1982 ◽  
Vol 52 (5) ◽  
pp. 1368-1374 ◽  
Author(s):  
V. B. Elings ◽  
F. R. Lewis ◽  
J. Briggs
Keyword(s):  
Extravascular Lung Water ◽  
Detection System ◽  
Indicator Dilution ◽  
Fluorescent Light ◽  
Left Heart ◽  
Lung Water ◽  
Fluorescent Indicator ◽  
Double Indicator Dilution

In vitro and in vivo indicator-dilution measurements are made with a fluorescent indicator and a novel detection system using a catheter containing a single optical fiber that carries both the exciting and returning fluorescent light. These fluorescent-dilution measurements are compared with simultaneous green dye-dilution measurements. The double-indicator-dilution measurement of extravascular lung water using heat and fluorescence is compared with gravimetric measurements. Also investigated is the sensitivity of the fluorescent measurement to changes in O2 saturation and hematocrit of the blood. An example of the measurement of a right-to-left heart shunt with this new indicator is given.

scholarly journals The Design and Preclinical Evaluation of a Single-Label Bimodal Nanobody Tracer for Image-Guided Surgery

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 360
Author(s):  
Pieterjan Debie ◽  
Noemi B. Declerck ◽  
Danny van Willigen ◽  
Celine M. Huygen ◽  
Bieke De Sloovere ◽  
...  
Keyword(s):  
Single Molecule ◽  
Gamma Ray ◽  
Nuclear Imaging ◽  
Primary Amines ◽  
Resection Margins ◽  
Fluorescent Light ◽  
Single Structure ◽  
Fluorescence Images

Intraoperative guidance using targeted fluorescent tracers can potentially provide surgeons with real-time feedback on the presence of tumor tissue in resection margins. To overcome the limited depth penetration of fluorescent light, combining fluorescence with SPECT/CT imaging and/or gamma-ray tracing has been proposed. Here, we describe the design and preclinical validation of a novel bimodal nanobody-tracer, labeled using a “multifunctional single attachment point” (MSAP) label, integrating a Cy5 fluorophore and a diethylenetriaminepentaacetic acid (DTPA) chelator into a single structure. After conjugation of the bimodal MSAP to primary amines of the anti-HER2 nanobody 2Rs15d and 111In-labeling of DTPA, the tracer’s characteristics were evaluated in vitro. Subsequently, its biodistribution and tumor targeting were assessed by SPECT/CT and fluorescence imaging over 24 h. Finally, the tracer’s ability to identify small, disseminated tumor lesions was investigated in mice bearing HER2-overexpressing SKOV3.IP1 peritoneal lesions. [111In]In-MSAP.2Rs15d retained its affinity following conjugation and remained stable for 24 h. In vivo SPECT/CT and fluorescence images showed specific uptake in HER2-overexpressing tumors with low background. High tumor-to-muscle ratios were obtained at 1h p.i. and remained 19-fold on SPECT/CT and 3-fold on fluorescence images over 24 h. In the intraperitoneally disseminated model, the tracer allowed detection of larger lesions via nuclear imaging, while fluorescence enabled accurate removal of submillimeter lesions. Bimodal nuclear/fluorescent nanobody-tracers can thus be conveniently designed by conjugation of a single-molecule MSAP-reagent carrying a fluorophore and chelator for radioactive labeling. Such tracers hold promise for clinical applications.

Involvement of αENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis

2007 ◽  
Vol 293 (4) ◽  
pp. L1069-L1078 ◽  
Author(s):  
Tianbo Li ◽  
Shyny Koshy ◽  
Hans G. Folkesson
Keyword(s):  
Extravascular Lung Water ◽  
Fluid Secretion ◽  
Alveolar Epithelial Cells ◽  
Na Channel ◽  
Fluid Absorption ◽  
Lung Water ◽  
Fourfold Increase ◽  
Lung Fluid ◽  
Near Term

To explore interactions between the epithelial Na channel (ENaC) and neural precursor expressed, developmentally downregulated protein 4-2 (Nedd4-2) at the conversion of the rat lung from fluid secretion to absorption at birth, we used small-interfering RNA (siRNA) against αENaC and Nedd4-2. siRNA-generating plasmid DNA (pDNA) was administered via trans-thoracic intrapulmonary (ttip) injection 24 h before ENaC and Nedd4-2 expression, extravascular lung water, and mortality were measured. αENaC mRNA and protein were specifically reduced by ∼65% after pSi-4 injection. Nedd4-2 mRNA and protein were reduced by ∼60% after pSi-N1 injection. Interestingly, αENaC and βENaC mRNA and protein expression were increased after Nedd4-2 silencing. Extravascular lung water was significantly increased after αENaC silencing and reduced after Nedd4-2 silencing. αENaC silencing resulted in a fourfold increase in newborn mortality, whereas silencing Nedd4-2 did not affect mortality. We also isolated distal lung epithelial (DLE) cells after in vivo αENaC or Nedd4-2 silencing and measured αENaC or Nedd4-2 expression in freshly isolated DLE cells. In these DLE cells, there were attenuated αENaC or Nedd4-2 mRNA and protein, thus demonstrating that αENaC and Nedd4-2 silencing occurred in alveolar epithelial cells after ttip injection. We also looked for pDNA by PCR to determine pDNA presence in the lungs and found strong evidence for pDNA presence in both lungs. Thus we provide evidence that ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.

scholarly journals Construction and Clinical Verification of Cytoplasm Protein GFAP as Circulating Tumor Cell Separation target for Pediatric Neuroepithelial Tumors

2020 ◽  
Author(s):  
Yang Zhao ◽  
Feng Jiang ◽  
Qinhua Wang ◽  
Baocheng Wang ◽  
Yipeng Han ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Detection System ◽  
Invasive Procedure ◽  
Circulating Tumor Cell ◽  
Immunofluorescence Assay ◽  
Good Choice ◽  
Neuroepithelial Tumors ◽  
Prediction Function

Abstract BACKGROUND: Pediatric Neuroepithelial Tumors (NT) are one of the most prevalent diseases among children. Developing a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function is very important. Circulating tumor cell (CTC) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTC separation target, an cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposomes (IMLs). The validation and efficiency of this system in capturing CTCs for NT were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. RESULTS: Our data show that CTCs can be successfully isolated from CSF and blood samples from 29 children with NT. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTC was consistant with tumor tissue. CONCLUSIONS: GFAP-IML isolation of CTCs, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique can be clinically significant in diagnosis and efficacy assessments of pediatric NT.

Endothelial extraction of tracer water varies with extravascular water in dog lungs

1987 ◽  
Vol 252 (2) ◽  
pp. H340-H348 ◽  
Author(s):  
F. P. Chinard ◽  
W. O. Cua
Keyword(s):  
Volume Of Distribution ◽  
Indicator Dilution ◽  
Lung Water ◽  
Limited Distribution ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator ◽  
The Time Domain ◽  
Area Product ◽  
Extravascular Volume

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels. We examine here the relations of the extraction of tracer water as tritium oxide (THO) [Ec(THO)] and of the extraction of tracer sodium as 22Na [Ec(22Na)] to extravascular lung water, delta V wev, by adding isotonic fluid to the gas phase of the lungs. The net convective transvascular passage of water is negligible relative to the transendothelial molecular exchange. In 10 experiments in vivo and in 10 experiments in isolated perfused lungs, Ec(THO) increases as delta V wev increases. Ec(22Na) and the permeability-surface area product (PS) for 22Na do not change as delta V wev increases. We conclude that the extraction of THO is determined mainly by the volume accessible to it (flow- or volume-limited distribution) and that the extraction of 22Na is determined mainly by the resistance of the endothelium (barrier-limited distribution). A diffusion limitation in the added alveolar fluid rather than a barrier limitation at the endothelium may moderate Ec(THO).

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