Reporter gene imaging: Effects of ganciclovir treatment on nucleoside uptake, hypoxia and perfusion in a murine gene therapy tumour model that expresses herpes simplex type-1 thymidine kinase
Bibliographic record
Abstract
Perfusion, hypoxia and nucleoside uptake during ganciclovir therapy were determined in a murine HSV-1 TK-expressing tumour model (KBALB-STK). HSV-1 TK mRNA transcription in this cell line was confirmed by RT-PCR. BALB/c mice bearing KBALB-STK tumours accumulated (E)-5-(2-[125I]iodovinyl)-2'-fluoro-2'-deoxyuridine ([125I]IVFRU) (2.54% injected dose.g-1) and could be readily detected with planar imaging following administration of [131I]IVFRU. However, a single dose of ganciclovir (100 mg.kg-1 intraperitoneally) decreased tumour uptake of [125I]IVFRU to 0.33% injected dose.g-1. Subsequent single daily doses of ganciclovir over 3 consecutive days had a negligible effect on [125I]IVFRU uptake, which remained low. Tumour perfusion during 3 days of ganciclovir treatment was monitored with intravenous [99Tcm]HMPAO. Tumour perfusion increased from day 0 (no ganciclovir treatment) with 1.83% injected dose.g-1 tumour, to a maximum at day 2 (3.77% injected dose.g-1). In the same animals, accumulation of [3H]misonidazole decreased from 0.70% injected dose.g-1 at day 0 to a minimum at day 3 (0.24% injected dose.g-1), indicating that tumour tissue had become less hypoxic over the ganciclovir regimen. The uptake of [125I]IVFRU into the acid insoluble fraction of KBALB-STK cells in vitro in the presence of ganciclovir (2.0 microM) was completely inhibited, leading to a 57% decrease in total cellular accumulation of radioactivity. However, cytosolic entrapment of [125I]IVFRU was not affected by the presence of ganciclovir. These results indicate that the mechanisms leading to IVFRU exclusion during ganciclovir treatment of HSV-1 TK-expressing tumours can be attributed, at least partially, to inhibition of [125I]IVFRU-nucleotide incorporation into DNA.
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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) | 0.001 | 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".