Radiolabeling of fab and f(ab′)2 antibody fragments with 99mTc(I) tricarbonyl core using a new bifunctional tridentate ligand
Bibliographic record
Abstract
The objective of this study was to design and evaluate a new histidine-modified tridentate chelator for labeling antimesothelin fab and f(ab')2 antibody fragments with the Tc(I) tricarbonyl ([Tc(CO)3]) core. N-(ortho-phenol)-histidine chelator was synthesized by modifying the single amino acid L-histidine, a natural amino acid, with an additional phenol group to obtain the bifunctional tridentate ligand after reductive amination. Bioconjugation was based on the carbodiimide activation of the carboxylate of chelator and on further reaction with the amine groups present on the antibody fragments. Radiolabeling was accomplished by replacing the three aqua ligands of the complex precursor [Tc(CO)3(H2O)3] with the tridentate chelator. The antibody fragments radiolabeled with [Tc(CO)3] core were tested for stability by the cysteine challenge test. The immunoreactivity and binding affinity of the radiolabeled fragments were studied using in-vitro cell-binding assays. Radiochemical yields achieved for [Tc(CO)3] core labeling of fab and f(ab')2 were 91.6±9.1% and 80.7±8.5%, respectively. Stability studies of radiolabeled antibody fragments showed that the Tc label was stable to transchelation by cysteine. Both Tc-fab and Tc-f(ab')2 retained their reactivity and affinity to the mesothelin antigen. From our studies, it can be concluded that the newly synthesized N-(ortho-phenol)-histidine chelator is a promising candidate for [Tc(CO)3] labeling of biomolecules and for developing other novel Tc radiopharmaceuticals.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 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".