The Cytotoxic Effect of 64Cu/NOTA-Terpyridine Platinum Conjugate, as a Novel Chemoradiotherapy Agent
Bibliographic record
Abstract
Colorectal cancer is one of the most prevalent cancers worldwide that displays both intrinsic and acquired resistance to platinum-based chemotherapeutic agents (Pt-CAs). To overcome such resistance, new classes of Pt-CAs have been proposed, including terpyridine (TP) compounds that target the G-quadruplex tertiary structure of DNA. Additionally, recent studies indicate a maximum chemoradiation benefit when radiation is administered with Pt-CAs at their highest concentrations in cancer cell DNA. Accordingly, we synthesized a novel chemo-radiotheranostic agent by conjugating a TP moiety with 64Cu (64Cu-NOTA-TP). The in vitro cytotoxic effects, cellular uptake, internalization and efflux of 64Cu-NOTA-TP were measured for colorectal cancer (HCT116) and normal fibroblast (GM05757) cells. Radiolabeling NOTA-TP with 64Cu resulted in 17,530-, 40,083- and 66,000-fold enhancements in its cytotoxicity against HCT116 cells (EC50 = 0.017 ± 0.004, 0.012 ± 0.006 and 0.005 ± 0.0002 µM) as compared to coldCu-NOTA-terpyridine (EC50 = 298 ± 2, 481 ± 25 and 330 ± 51 µM) at 24, 48 and 72 h post-administration, respectively. More importantly, the cytotoxicity of the 64Cu-conjugate toward the HCT116 cells was about 3.8-fold higher than that of GM05757 cells at 24 and 72 h. This result was consistent with a 2–3-fold higher internalization of 64Cu-conjugate in HCT116 cells relative to GM05757 cells at similar times. The internalized activity of the 64Cu-conjugate steadily increased from 0.04 ± 0.02% to 18.7 ± 2.8% over a 24 h incubation time. Moreover, the efflux kinetics of the 64Cu-conjugate showed that more than 40% of internalized activity was retained by cancer cells over a 24 h period. In conclusion, this work presents a novel chemo-radiotherapeutic agent with considerable potential for targeted cancer treatment combined with radioisotope imaging.
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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 | 0.000 |
| 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 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".