In-vitro cytotoxic effect of 64Cu/NOTA-terpyridine platinum conjugate, as a novel theranostic agent
Bibliographic record
Abstract
1615 Objectives: Recent advances in the field of nuclear medicine have allowed the development of several metal-based compounds for cancer diagnosis and treatment. There is a considerable enthusiasm to improve the efficacy of radiotherapy protocols through synthesizing new metal-based compounds with lower toxicity for normal tissues. Here, we have synthesized 64Cu-NOTA terpyridine platinum conjugate as a novel bi-metallic agent that is tailored toward quadruplex motifs on DNA. Our objective is to demonstrate that such theranostic agent could give rise to greater selectivity for cancer cells. Methods: The in-vitro cytotoxic effect, cell uptake, internalization and efflux of 64Cu-NOTA terpyridine platinum complex and other control compounds were tested on a colorectal cancer cell (HCT116) as well as a normal fibroblast cell line (GM05757) at 24, 48 and 72 hours after initial incubation time. Results: natCu-labeled NOTA-terpyridine platinum complex showed 3.35, 1.74 and 2.26 times higher cytotoxicity against HCT116 cells as compared to GM05757 normal cells. However, the cytotoxic effects of our complex (IC50 = 298.2 - 481 µM) was much less than cisplatin (IC50 = 23.3 - 41.6 µM). Remarkably, removal of natCu from our complex (NOTA-terpyridine platinum) increased its activity against HCT116 cells from 7.63 (IC50=63±1.08µM) to 13.53 (IC50=24±1.25µM) folds, suggesting considerable influence of charge on cytotoxicity of the complex. The internalization of 64Cu-NOTA terpyridine platinum complex in HCT116 cells increased from 15 min (0.04±0.021%) to 24h (18.7±2.77%) and reached a plateau at 48h (18.6±1.45%), post-administration. The percentages of internalization were significantly higher in HCT116 cancer cells as compared to GM05757 normal cells at 24h, 48h and 72h post-administration (Pvalue
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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) | 0.001 | 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".