Evaluation of an <SUP>18</SUP>F-Labeled Oligonucleotide Probe Targeting <I>p21<SUP>WAF1</SUP></I> Transcriptional Changes in Human Tumor Cells
Bibliographic record
Abstract
The ability to image gene expression using 18F-labeled antisense oligonucleotides (asODNs) directed to specific mRNA transcripts during, or immediately following, radio- or chemotherapy would be a valuable clinical tool to monitor the early tumor response to treatment. Imaging of upregulated p21 mRNA postirradiation using 18F-labeled asODNs could offer insights into early tumor responses by detecting signs of accelerated cellular senescence. Thus, the aim of this work was to evaluate the uptake and distribution of a (radio)-fluorinated asODN in vitro in HCT116 p21(+/+) human colon carcinoma cells, asODN and a random sequence oligonucleotide (rsODN) were conjugated with a (radio)fluorine prosthetic group. Irradiated HCT116 cells were treated with naked or liposome-transfected ODNs. Cell fractionation, confocal microscopy, immunofluorescence, and Western blot studies were performed to observe uptake, distribution, and antisense activity of the probes. [F]asODN demonstrated similar antisense binding ability as the unlabeled asODN to p21 mRNA. Liposomal-transfected 18F-labeled asODNs and rsODNs exhibited a three-to fivefold increase in uptake at 2.5 h compared to the naked [18F]ODNs. Distribution of transfected [18F]asODN in the cytoplasm and endosomes increased over time whereas no change in intracellular distribution was observed with transfected [18F]rsODN or naked ODNs. Antisense activity was not compromised with the addition of a fluorine moiety on asODN. The cellular accumulation and distribution of the (radio)fluorinated ODNs was not altered by the addition of the prosthetic group. Radiolabeled ODNs were able to penetrate the cell with preferential uptake observed with the liposome-transfected probes. Increased distribution of [18F]asODN in the cytoplasm suggests the probe is available for targeting its transcript mRNA. This warrants further investigations into the potential of [18F]asODN to image accelerated senescence postirradiation.
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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 | 0.017 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| 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".