<sup>225</sup> Ac/ <sup>89</sup> Zr-Labeled N4MU01 Radioimmunoconjugates as Theranostics Against Nectin-4–Positive Triple-Negative Breast Cancer
Bibliographic record
Abstract
Nectin-4 is an overexpressed biomarker in 60%–70% of triple-negative breast cancer (TNBC) cases and an ideal target for radiotherapy and PET imaging. In this study, theranostic radioimmunoconjugates were developed using a fully human anti–nectin-4 antibody (N4MU01). The imaging properties and therapeutic effectiveness of the radioimmunoconjugates were evaluated using TNBC models. Methods: N4MU01 was radiolabeled with 89Zr and 225Ac for imaging and radiotherapy, respectively, using TNBC xenograft and syngeneic models. Biodistribution and PET imaging of the [89Zr]Zr-deferoxamine (DFO)-N4MU01 radioimmunoconjugate was studied in mice bearing nectin-4–positive xenografts. Dosimetry and toxicity of [225Ac]Ac-Macropa-N4MU01 were studied in naïve BALB/c mice, and the therapeutic efficacy was evaluated with two doses of 13 or two doses of 18.6 kBq, administered 10 d apart in athymic BALB/c nude mice bearing either a human TNBC MDA-MB-468 xenograft or a human nectin-4–transfected 4T1 (4T1.nectin-4) syngeneic allograft. Results: The pharmacokinetic profile of the [89Zr]Zr-DFO-N4MU01 radioimmunoconjugate showed biphasic distribution with a moderate elimination half-life of 63 h. PET imaging and biodistribution of [89Zr]Zr-DFO-N4MU01 in mice bearing the MDA-MB-468 xenograft showed high tumor uptake of 13.2 ± 1.12 percent injected activity per gram at 120 h. [225Ac]Ac-Macropa-N4MU01 was effectively internalized in MDA-MB-468 and was cytotoxic to the cells with a 50% inhibition concentration of 1.2 kBq/mL. Toxicity studies revealed that 15 kBq of [225Ac]Ac-Macropa-N4MU01 was generally well tolerated, as indicated by hematologic, blood chemistry, and histopathologic analysis. Mice bearing MDA-MB-468 and 4T1.nectin-4 xenografts treated with 13 kBq of [225Ac]Ac-Macropa-N4MU01 had 100% (6/6) and 83.3% (5/6) complete tumor remissions, respectively. Conclusion: The specific tumor uptake and remarkable effectiveness against aggressive TNBC tumors are very promising and warrant the clinical development of N4MU01 radioimmunoconjugates.
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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".