Abstract 206: Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer cells
Bibliographic record
Abstract
Abstract Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer cells OBJECTIVE: Molecular imaging plays an important role in oncology for staging of tumors. Unfortunately, the specificity and sensitivity of current techniques remains low. This study aims to improve the existing imaging system based on transcriptional activation, named as “Two -Step- Transcriptional Amplification (TSTA) system”, with the goal to precisely image in vivo prostate cancer cells (PCa) by Positron Emission Tomography (PET). We have studied the potential of DD3/PCA3 promoter, a gene specifically expressed in PCa, to achieve this goal. METHODS: Various adenovirus constructs incorporating the DD3 promoter, the TSTA system and the Firefly luciferase reporter gene were generated and their specificity for PCa cells was tested in transient infection. By molecular engineering, we have improved the TSTA system and generated the 3STA. The luciferase activities of DD3-TSTA, DD3-3STA and PSA-TSTA (Prostate Specific Antigen) were compared in vivo by bioluminescence in xenograft mouse models. Ex vivo prostate biopsy from RP (radical prostatectomy) specimen were exposed to DD3-3STA and luciferase expression was evaluated using bioluminescence and Immunohistochemistry. RESULTS: The DD3 promoter activity is both specific to prostate and cancer cells. When DD3 promoter is incorporated in the amplification systems TSTA and 3STA, it is specific to PCa cells and its activity is amplified 32 and 95 times, respectively, when compared to the activity of the DD3 promoter alone. Moreover, activity of DD3-TSTA and DD3-3STA is androgen-independent. In vivo, DD3-3STA activity is comparable to that obtained with the PSA-TSTA whose activity can be imaged by PET. DD3-3STA could detect primary prostate cancer cells ex vivo in prostate biopsy obtained from RP specimen (Figure 1). CONCLUSIONS: The new system DD3-3STA allows specific and sensitive imaging of PCa cells. The new amplification system 3STA allows the DD3 promoter to produce reporter signal high enough to be detected by PET, a technology available in the clinic. Citation Format: Pallavi Jain, Bertrand Neveu, Yves Fradet, Frederic Pouliot. Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 206. doi:10.1158/1538-7445.AM2015-206
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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) | 0.000 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".