Intratumoral localization kinetics of Foslip® using two photon confocal microscopy: corelation with photodynamic efficiency
Bibliographic record
Abstract
Background: Photodynamic therapy (PDT) requires a combination of photosensitizer (PS), light and oxygen to produce cytotoxic species. The tumor vasculature and neoplastic cells in the parenchyma are two potential targets of PDT. The distribution of PS in different compartments can be adjusted by changing the interval between the administration of drugs and irradiation (DLI). The efficiency of PDT is closely correlated with the distribution of PS in each compartment at the time of treatment. Objective: The objective of this work is to determine the Foslip® localization kinetics within the tumor then correlate this localization to the treatment efficacy. Method: The model used was a xenografted nude mice (EMT6 cells). The PS intra-tumor localization has been achieved by two-photon laser scanning confocal microscope (TPLSCM). The evaluation of the efficiency of PDT was performed by measuring tumor regrowth after treatment. Results: TPLSCM enables the ex-vivo localization of PS in the tumor. A localization kinetic was made from 15 min to 24 h after injection. For short intervals of 15 minutes and 1 hour , the photosensitiser was strictly confined to the vessels. For 3 hours DLI, the drug fluorescence starts to diffuse into the nearby tissues. mTHPC fluorescence distribution pattern at six hours after administration was characterized by its localization in tumour and endothelial cells. For 15 and 24 h post injection, the fluorescence arises from the tumour cells and is most pronounced at a remote distance from the vessels. The best PDT efficiency was obtained for DLI of 6 hours, time for which the localization of PS is clearly seen in tumor and endothelial cells. This highlights the destruction of tumors by Foslip®-PDT by a combination of direct effect on cancer cells and by a vascular effect. Conclusion: These results demonstrates the significance of the spatial and temporal intratumor distribution of PDT so that better informed clinical protocols can be initiated. The two photon confocal fluorescence imaging technique used here provides an excellent tool to study the intratumor distribution of not only other PS but also of chemotherapy agents, which share common physiological barriers in their transport from the vessels through the extravascular space to reach the tumor cells.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".