Biodistribution of near-infrared emitting CuInS2/ZnS Quantum Dots by mass spectroscopy and fluorescence imaging of sentinel lymph node in mice
Bibliographic record
Abstract
Background: The biopsy of the sentinel lymph nodes in breast cancer patients is now strongly recommended for the definition of the further therapeutic strategy. Although this approach has strong advantages, it has its own limitations (manipulation of radioactive products and possible anaphylactic reactions to the dye). As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the in vivo imaging of sentinel lymph nodes [1]. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient and good quantum yield [2]. Most synthesized QDs are composed of toxic heavy metals (Cd, Te, Se,...) and as such could not be used in the clinical context. Recently, we have demonstrated excellent imaging properties of Cd-free QDs for in vivo lymph nodes detection along with the greatly diminished acute inflammation in healthy rodents [3, 4]. Far before the clinical settings could be envisaged, the study on biodistribution of CuInS2/ZnS QDs in pre-clinical models and the possibility of visualization of lymph nodes upon metastatic dissemination is mandatory. Material and Methods: In vitro studies: The toxicity of CuInS2/ZnS core/shell QD on red blood cells has been tested using the haemolysis test. Red blood cells were incubated during 2h with different concentration of QDs and the release of haemoglobin was measured by spectrophotometry. In vivo studies: Healthy or tumor-bearing mice received 20 μL of 1 μM CuInS2/ZnS core/shell QD solution subcutaneously in the right anterior paw. Right axillary lymph nodes (RALN) were visualized using a near-infrared imaging system (Fluobeam™) and healthy animals were sacrificed at different time points after QDs injection. Organs, blood and excretions were collected and their indium content was measured by ICP-MS. The sentinel lymph node of tumor-bearing mice was imaged by fluorescence and the metastatic involvement of lymph nodes was assessed by the measurement of cytokeratin 19 by RT-qPCR or immunohistochemistry. Results and Discussion: In vitro assessed toxicity: No haemolysis of red blood cells was detected in the range of concentrations of CuInS2/ZnS QDs from 25 to 150 nM, while Cd-based QDs induced 50% of hemolysis with already 56.3 nM (data not shown). In vivo studies: CuInS2/ZnS QDs were observed in RALN as soon as 5 min (Fig. 1) and up to 7 days after the subcutaneous injection of QD in the right anterior paw by in vivo NIR fluorescence imaging.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".