Intratumoral 18F-FLT infusion in metabolic targeted radiotherapy
Bibliographic record
Abstract
The goal of targeted radiotherapy (TRT) is to administer radionuclides to tumor cells, while limiting radiation exposure to normal tissues. 3′-Deoxy-3′-[ 18 F]-fluorothymidine ( 18 F-FLT) is able to target tumor cells and emits a positron with energy appropriate for local (~ 1 mm range) radiotherapy. In the present work, we investigated the potential of TRT with a local administration of 18 F-FLT alone or in combination with 5-fluorouracil (5FU), which acts as a chemotherapeutic agent and radiosensitizer. Treatment efficiency of 18 F-FLT combined or not with 5FU was evaluated by intratumoral ( i.t. ) infusion into subcutaneous HCT116 colorectal tumors implanted in nu/nu mice. The tumor uptake and kinetics of 18 F-FLT were determined and compared to 2-deoxy-2-[ 18 F]-fluoro-D-glucose ( 18 F-FDG) by dynamic positron emission tomography (PET) imaging following i.t. injection. The therapeutic responses of 18 F-FLT alone and with 5FU were evaluated and compared with 18 F-FDG and external beam radiotherapy (EBRT). The level of prostaglandin E 2 (PGE 2 ) biosynthesis was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in order to determine the level of inflammation to healthy tissues surrounding the tumor, after i.t. injection of 18 F-FLT, and compared to EBRT. We found that i.t. administration of 18 F-FLT offers (1) the highest tumor-to-muscle uptake ratio not only in the injected tumor, but also in distant tumors, suggesting potential for concurrent metastases treatment and (2) a sixfold gain in radiotherapeutic efficacy in the primary tumor relative to EBRT, which can be further enhanced with concurrent i.t. administration of the radiosensitizer 5FU. While EBRT stimulated PGE 2 production in peritumoral tissues, no significant increase of PGE 2 was measured in this area following i.t. administration of 18 F-FLT. Considering the biochemical stability of 18 F-FLT and the physical properties of localized 18 F, this study shows that TRT via intratumoral infusion of 18 F-FLT and 5FU could provide a new effective treatment option for solid tumors. Using this approach in a colorectal tumor model, the tumor and its metastases could be efficiently irradiated locally with much lower doses absorbed by healthy tissues than with i.t. administration of 18 F-FDG or conventional EBRT.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| 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".