Positron Emission Tomography/Computed Tomography (PET/CT) and Radioimmunotherapy of Head and Neck Cancer Patient Derived Xenografts in NRG Mice with Theranostic [ <sup>64</sup> Cu]Cu-DOTA-Panitumumab F(ab′) <sub>2</sub> and [ <sup>177</sup> Lu]Lu-DOTA-Panitumumab F(ab′) <sub>2</sub>
Bibliographic record
Abstract
Head and neck squamous cell carcinoma (HNSCC) expresses epidermal growth factor receptors (EGFR) in 90% of cases. Here we studied PET/CT imaging of three clinically relevant HNSCC patient derived xenografts (PDX) with low (#61531), moderate (#73191) or high (#88955) EGFR expression in NRG mice using anti-EGFR [ 64 Cu]Cu-DOTA-panitumumab F(ab′) 2 . We further assessed the effectiveness of β-particle-emitting [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 for radioimmunotherapy (RIT) of these PDX. All PDX were visualized by PET/CT at 24 h postinjection (p.i.) of [ 64 Cu]Cu-DOTA-panitumumab F(ab’) 2 . In addition, in mice with PDX #88955, an axillary lymph node metastasis was imaged by PET and lung metastases were imaged by SPECT/CT at 3 to 12 d p.i. of [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 . Tumor uptake of [ 64 Cu]Cu-DOTA-panitumumab F(ab′) 2 at 24 h p.i. was directly correlated with EGFR expression (6.7 ± 3.5%, 13.5 ± 2.5% and 16.7 ± 1.0% ID/g for PDX #61531, #73191 and #88955, respectively). Intravenous administration of 5.0 MBq (50 μg) of [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 to healthy NRG mice caused no hematologic, liver or kidney toxicity or decrease in body weight. RIT with 4.0–5.0 MBq (50 μg) of [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 decreased the tumor growth rate vs 0.9% NaCl by 2, 9 and 3.2-fold, respectively in mice with PDX #61531, #73191 and #88955 ( P = 0.014, P < 0.001, P = 0.004). Treatment of mice with unlabeled DOTA-panitumumab F(ab′) 2 did not decrease the tumor growth rate of PDX#61531 ( P = 0.457) but modestly decreased the tumor growth rate of PDX #73191 by 1.3-fold ( P = 0.024) and PDX #88955 by 1.4-fold ( P = 0.027). RIT was EGFR-specific as irrelevant anti-HER2 [ 177 Lu]Lu-DOTA-trastuzumab F(ab′) 2 was not effective for treatment of PDX #73191 vs 0.9% NaCl ( P = 0.282). RIT with [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 was 3-fold more effective for treating moderately EGFR-expressing PDX #73191 than PDX #88955 with high EGFR expression. This may be explained by the human papilloma virus (HPV) positivity of PDX #73191 since HPV-positive HNSCC is more responsive to external radiation beam treatment. We conclude that [ 64 Cu]Cu-DOTA-panitumumab F(ab′) 2 and [ 177 Lu]Lu-DOTA-panitumumab F(ab′) 2 are a promising theranostic pair for PET/CT imaging and RIT of HNSCC.
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How this classification was reachedexpand
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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".