Abstract 3258: Imaging HER-2 positive breast cancer tumors with trastuzumab radiolabeled with DOTA, Oxo and PCTA and positron emission tomography (PET)
Notice bibliographique
Résumé
Abstract Introduction: Monoclonal antibodies (mAbs) are attractive vectors in the development of diagnostic imaging agents because of their specificity. Labeled with the appropriate radioisotope, mAbs can be used to monitor expression levels of a cell surface receptor non-invasively. The data can be used to stratify or monitor patients for/during targeted chemotherapy therapy. We report here the use of trastuzumab labeled with DOTA, a widely used bifunctional chelate (BFC), and two novel BFCs (Oxo and PCTA), to image HER-2 receptor expression non-invasively in a breast cancer model with PET. Materials and Methods: The BFCs were incubated with trastuzumab in HEPES buffer (50mM, pH 8.5, 20 h), the bioconjugates purified by column chromatography, and radiolabeled with Cu-64 in sodium acetate buffer (40 - 400 MBq, 10 mM, pH 5.5, 0.5 - 2 h). The specificity of the DOTA, Oxo, and PCTA bioconjugates for the HER-2 receptor, and cellular uptake were verified in HER-2 positive cell lines using flow cytometry and scintigraphy, respectively. The PET imaging characteristics and biodistribution of the Cu-64 bioconjugates were examined in HER-2 positive and negative breast cancer tumors grown in mice with the Siemens Inveon Multi-Modality PET-CT animal scanner at 24 and 40h post-injection. Results: The specificity of trastuzumab to the HER-2 receptor was unchanged by conjugation to DOTA, Oxo or PCTA. The range of specific activities (GBq/micromol)of Cu-64 radiolabeled Oxo (49 -100) and PCTA (52-70) were higher than DOTA (46 -47). Radiochemical yields ranged from 23 - 88%, 55- 97% and 50-98% for DOTA, Oxo and PCTA, respectively. In vitro uptake of trastuzumab labeled with Cu-64 by the three BFCs was high in HER-2 positive cells (33 - 44% Cu-64 dose), but negligible in HER-2 negative cells. The tissue biodistribution of all three radiolabeled conjugates were similar; uptake in the HER-2 positive tumors was higher than in the control tumors (p<0.01) as expected at 24 and 40h. However, there was significantly higher uptake of the PCTA and Oxo bioconjugates compared to DOTA (p = 0.014 and p = 0.006, respectively) at the earlier timepoint. The corresponding tumor to background ratios for PCTA and Oxo-trastuzumab were also higher that those for DOTA-trastuzumab. PET images and region of interest analysis show that the Cu-64 labeled bioconjugates of DOTA, Oxo and PCTA accumulate preferentially in HER-2 positive tumors at 24 and 40h. However, visualization of the tumors was clearer with Cu-64 labeled bioconjugates of Oxo and PCTA, compared to DOTA. Conclusions: The novel bifunctional chelates PCTA and Oxo radiolabel Cu-64 more efficiently and rapidly than DOTA under mild conditions. All three radiolabeled conjugates of trastuzumab were specific for the HER-2 receptor in a mouse model for HER-2 positive breast cancer, but the data indicate that tumors can be visualized earlier with Oxo and PCTA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3258.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».