Intratumorally Injected <sup>177</sup>Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
UNLABELLED: Improvements in the treatment of locally advanced breast cancer (LABC) are needed. Our objective was to study a radiation nanomedicine (gold nanoseeds) composed of 30-nm gold nanoparticles (AuNP) modified with polyethyleneglycol (PEG) chains linked to DOTA for complexing the β-particle emitter (177)Lu and to panitumumab for targeting epidermal growth factor receptors (EGFR) ((177)Lu-T-AuNP) as a novel neoadjuvant brachytherapy for LABC. Nontargeted gold nanoseeds ((177)Lu-NT-AuNP) were constructed without panitumumab for comparison. METHODS: (177)Lu-T-AuNP or (177)Lu-NT-AuNP was injected intratumorally in CD-1 athymic mice bearing subcutaneous EGFR-positive MDA-MB-468 human breast cancer tumors. Biodistribution and small-animal SPECT/CT imaging studies were performed to evaluate tumor and normal organ localization. A short-term (15 d) study was conducted to select the most effective amount of (177)Lu-T-AuNP or (177)Lu-NT-AuNP for treatment with long-term observation (90-120 d). Normal organ toxicities were assessed by monitoring body weight, blood cell counts, and serum alanine aminotransferase and creatinine. Radiation-absorbed doses in the tumor and normal organs were estimated by Monte Carlo N-Particle version 5.0 modeling. RESULTS: Tumor radioactivity concentrations were high at 1 h after injection (>300-400 percentage injected dose per gram [%ID/g]) but decreased by 2-3-fold at 48 h after injection. Normal organ uptake was low (<0.5 %ID/g) except for the liver and spleen (<3 %ID/g), increasing by 2-5-fold at 48 h after injection. Treatment with 4.5 MBq (6 × 10(11) AuNP) of (177)Lu-T-AuNP or (177)Lu-NT-AuNP arrested tumor growth over 90 d without normal organ toxicity, whereas tumors continued to grow in mice treated with unlabeled T-AuNP or (177)Lu-labeled PEG polymer not linked to AuNP. Survival was prolonged up to 120 d in mice treated with (177)Lu-T-AuNP or (177)Lu-NT-AuNP. Radiation-absorbed doses to the tumor were 30 and 22 Gy for (177)Lu-T-AuNP and (177)Lu-NT-AuNP, respectively. Some tumor regions received high radiation doses (250-1,300 Gy). Normal organ doses were low (0.04-0.6 Gy). CONCLUSION: Gold nanoseeds injected intratumorally were highly effective for inhibiting the growth of breast cancer tumors in CD-1 athymic mice and caused no normal organ toxicity. These results are promising for their application for neoadjuvant brachytherapy of LABC. Because EGFR targeting was not required, the approach is broadly applicable to LABC with different phenotypes.
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.
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) | 0.001 | 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 it