DEVELOPMENT AND PRECLINICAL VALIDATION OF AN ANTI-EDNRB IMMUNOPET PROBE FOR MELANOMA IMAGING
Bibliographic record
Abstract
Melanoma comprises only 1-2% of skin cancer cases, but it is responsible for 90% of mortality from this disease. Global incidence has also been drastically increasing for the last century, with cases doubling every 10-20 years. Melanoma’s high propensity to metastasize is the major cause of mortality, as primary melanoma is relatively manageable, with 5-year survival rates >98%. [18F]-fluorodeoxyglucose positron emission tomography is the current state of the art for detecting metastases, disease staging, recurrence, and monitoring response to treatment. However, the general specificity this probe has for glucose metabolism and not melanoma itself results in off-target uptake in other glucose avid processes, like inflammation (false positives), and low/indeterminate uptake in small or metabolically inactive metastases (false negatives). To address this issue, a melanoma-specific immunoPET probe, [89Zr]Zr-DFO-3H5, was developed in collaboration with the National Research Council of Canada. The following work describes the development and preclinical validation of [89Zr]Zr-DFO-3H5. The antibody, 3H5, targets endothelin receptor type B, which is overexpressed in metastatic melanoma in comparison to both healthy tissues and other cancers. Zirconium-89, linked to the antibody via the bifunctional chelator DFO (deferoxamine), can then be delivered to metastatic sites, where it can emit positrons used in PET imaging. In preclinical in vivo PET imaging and biodistribution studies, the probe successfully and specifically delineated implanted tumours, demonstrating high tumour uptake (24.88 %ID/g), favourable biodistribution (<8 %ID/g in off-target tissues), and promising tumour-to-muscle (89.3), tumour-to-heart (7.2), and tumour-to-liver ratios (3.3). Specificity was shown by a decrease in uptake in a blocked control cohort (13.40 %ID/g) and in another control cohort that received a probe analog comprising a non-specific antibody (4.40 %ID/g). These promising early data warrant the continued investigation and validation of this probe as a radiopharmaceutical with the potential to improve upon metastatic melanoma imaging.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".