Molecular Imaging and Treatment of Malignant Gliomas Following Adenoviral Transfer of the Herpes Simplex Virus-Thymidine Kinase Gene and the Somatostatin Receptor Subtype 2 Gene
Bibliographic record
Abstract
Patients suffering from malignant glioma have a very poor prognosis. New therapy approaches for gliomas are necessary; these tumors are attractive targets for gene therapy. Our research concentrated on evaluation of the use of the Herpes Simplex Virus-thymidine kinase (tk) enzyme and the somatostatin receptor subtype 2 (sst2). DOTA-Tyr3-octreotate is an analog of somatostatin with high affinity for sst2. It shows rapid internalization in sst2-positive tumor cells in vitro and in vivo. For gene therapy, we used the adenoviral vector Ad5.tk.sstr, which carries the tk gene and the sst2 gene. The aim of our study was to compare uptake of the tk substrate 1-(2-fluoro-2-deoxy-beta-D-ribofuranosyl)-5-[*I]iodouracil (FIRU) labeled with 125I and the somatostatin analog 111In-DOTA-Tyr3-octreotate in several glioma cell lines after infection with Ad5.tk.sstr. Uptake of 125I-FIRU was measured in rat 9L-tk glioma cells without infection with Ad5.tk.sstr. Results showed that the uptake of 125I-FIRU was concentration and time dependent. We also used several rat and human glioma cell lines for infection with Ad5.tk.sstr. Forty-eight hours after infection, uptake studies were performed using 125I-FIRU and 111In-DOTA-Tyr3-octreotate. In all cell lines, the uptake of 125I-FIRU and 111In-DOTA-Tyr3-octreotate increased with increasing multiplicity of infection of virus and showed that the uptake of 111In-DOTA-Tyr3-octreotate was higher than that of 125I-FIRU in all cell lines. We conclude that the sst2 imaging and therapy modality is most promising for glioma gene therapy, either alone or in combination with HSV-tk suicide gene therapy. Therapy can be performed using combinations of DOTA-Tyr3-octreotate radiolabeled with 177Lu or 90Y, 131I-FIRU and/or the prodrug ganciclovir.
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 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 | 0.000 | 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 | 0.001 |
| 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".