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 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 | 0.001 | 0.001 |
| 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".