Molecular Imaging of Murine Acute Lung Inflammation Using 89 Zr-labeled Angiostatin
Bibliographic record
Abstract
Abstract Angiostatin (ANG) is an endogenously cleaved protein of plasminogen-plasmin which is activated not only during tumor angiogenesis but also during acute inflammation such as in acute lung injury (ALI). Murine tumors concentrate radioactive iodine labelled angiostatin, but there is a lack of information about its distribution in ALI. Therefore, the present study was performed to understand the distribution of radiolabeled neutrophil elastase-derived ANG (89Zr-ANG) in a combined ozone and LPS induced murine ALI. Pharmacokinetic evaluation was performed through 3-day sequential microPET/CT, followed by whole-body and fractionated blood biodistribution studies. Data analysis also accounted for differential sex-based biodistribution of 89Zr tagged angiostatin. Standard uptake ratio (SUR) of 89Zr-ANG in lungs was up to 4.8-8.5 and 4.2-11.6-fold higher in male and female mice, respectively (studied at 24, 48 and 72 h) after ozone and LPS treatment compared with sham-operated groups (p<0.0001). The biodistribution showed that after ozone and LPS treatment, both male and female mice recorded higher radioactivity counts in kidneys, lungs, thyroid, skull, small intestine, spleen, tail, pancreas, the platelet fraction of whole blood and also in the uterus of female mice when compared to sham-operated group. We also tested prognostic significance of 89Zr labeled angiostatin against an established inflammation marker 68Ga-citrate, using PET/CT in our murine ALI model. SUR of 68Ga-citrate in lungs of mice was 1.10-4.60-fold higher in both sexes at 0, 24 and 48 h following ozone and LPS treatment compared with their respective pre-treatment SUR. Lung 68Ga-citrate peaked at 48 h after treatment indicating maximum vascular permeability. Fluorescent dye (CF-488) labeled angiostatin was injected along with 68Ga-citrate to confirm our earlier observation of 89Zr-ANG accumulation in platelets. Both ex-vivo and in-vitro results indicated that activated platelets preferentially bind angiostatin compared to untreated platelets for up to 72 h through high affinity lysine binding sites. Preliminary in vitro data from pig platelets confirm the murine angiostatin binding pattern. Future studies in porcine ALI model will help translate the findings from mouse experiments to humans. Thus, the current study supports the use of 89Zr-ANG as a PET tracer for imaging platelet activation in murine ALI. Keywords: ozone; LPS; lung inflammation; angiostatin; molecular imaging; platelets
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".