Abstract C293: Irinotecan sucrosofate liposome injection, MM-398, demonstrates superior activity and control of hypoxia as measured through longitudinal imaging using [18F]FAZA PET compared to free irinotecan in a colon adenocarcinoma xenograft model.
Notice bibliographique
Résumé
Abstract Tumor hypoxia is strongly linked to aggressive disease progression and resistance to therapy. Positron emission tomography (PET) imaging with hypoxia tracers such as [18F]fluoroazomycin arabinoside (FAZA) allows for non-invasive quantification of tumor hypoxia during treatment. We and others have previously shown by immunohistochemical methods that treatments with longer lasting camptothecin formulations reduce tumor hypoxia after either single or multiple treatment cycles. Here we evaluated the kinetics and magnitude of hypoxia changes in tumors after treatment with irinotecan sucrosofate liposome injection (MM-398) which has shown an extended plasma half-life and higher intratumoral deposition in animal models relative to free pro-drug and compare it to the effects of free irinotecan at equivalent exposure levels. FAZA-PET/CT was used for longitudinal monitoring of tumor hypoxia changes in the HT29 mouse colon cancer xenograft model over a 21-day period following weekly chemotherapy administrations of either MM-398 (5 & 10mg/kg) or free irinotecan (50mg/kg). These dosages were predicted to result in comparable SN-38 exposure in either plasma or tumor based on a mechanistic pharmacokinetic model of MM-398 and free irinotecan that was developed using a systems pharmacology approach. Baseline levels of FAZA uptake in tumors were similar across treatment groups. Significant differences in tumor FAZA uptake were observed between these groups as early as Day 7 post treatment initiation, with increased FAZA uptake seen in tumors treated with free irinotecan. In contrast, differences in tumor volume only became statistically significant on Day 16. MM-398 at 10mg/kg was the most effective treatment for control of tumor volume and also minimized changes in FAZA uptake at all time-points. Background FAZA levels in the muscle were consistent over time across all treatment groups (0.78±0.18 %ID/g, 0.81±0.11 %ID/g and 0.71±0.20 %ID/g). However, normalization with muscle signal did not improve quantification of FAZA uptake differences in tumors. Tumor-specific hypoxia status at the study end point was confirmed by co-staining for CA9 and EF5 levels, which were, as expected, highly correlated. Average EF5 intensity/tumor area was lowest in the MM-398 (10mg/kg) treatment group, while being highest in the irinotecan (50mg/kg) treatment group. This study demonstrated the feasibility of performing longitudinal and repeated tumor hypoxia assessment using FAZA-PET imaging. Treatment with MM-398, but not free irinotecan, led to significant changes in the tumor microenvironment as measured by reduced hypoxia levels that occurred far earlier than anatomical changes assessed by tumor volume. Imaging of hypoxia levels after anti-cancer therapy with MM-398 has the potential to allow early assessment of treatment activity. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C293. Citation Format: Stephan G. Klinz, Jinzi Zheng, Raquel De Souza, Michael Dunne, Jason Cain, Jaeyeon Kim, Nancy Paz, Ashish Kalra, David Jaffray, Jonathan Fitzgerald. Irinotecan sucrosofate liposome injection, MM-398, demonstrates superior activity and control of hypoxia as measured through longitudinal imaging using [18F]FAZA PET compared to free irinotecan in a colon adenocarcinoma xenograft model. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C293.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,000 | 0,000 |
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 tête enseignante, 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 ».