Comparison of two high affinity gallium-68-labeled bradykinin receptor antagonists for in vivo imaging of bradykinin B1 receptor expression
Notice bibliographique
Résumé
113 Objectives The bradykinin B1 receptor (B1R) is a G protein-coupled receptor and is minimally expressed in normal tissues. Due to its overexpression in a variety of cancers, B1R is a promising cancer imaging biomarker. In this study, we synthesized and evaluated two B1R-targeting peptides, 68Ga-P05022 (68Ga-DOTA-Pip-B9858) and 68Ga-Z02176 (68Ga-DOTA-Pip-B9958), for imaging B1R expression with PET (Pip: 4-amino-(1-carboxymethyl)piperidine; B9858:Lys-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic; B9958: Lys-Lys-Arg-Pro-Hyp-Gly-Cpg-Ser-D-Tic-Cpg). Methods The DOTA-conjugated peptides were synthesized by solid phase peptide synthesis, and reacted with GaCl3 to obtain cold standards. B1R binding affinity was measured by in vitro competition binding assays. The peptides were labeled with 68Ga by microwave heating followed by HPLC purification. LogD7.4 values were determined via traditional shake flask method. PET/CT imaging and biodistribution studies were performed in NODSCID/IL2RKO mice bearing both B1R-negative (B1R-) HEK293T wild-type tumor and B1R-positive (B1R+) HEK293T::hB1R tumor. Blocking studies were performed by co-injecting the tracers with their respective cold standard (100 μg). Results P05022 and Z02176 were obtained with 12 % and 18 % overall yield. The binding affinities (Ki) of P05022 and Z02176 to hB1R were 5.5 ± 0.1 and 2.5 ± 0.8 nM, respectively. 68Ga-labeled P05022 and Z02176 were prepared in 42 - 76 % decay-corrected radiochemical yield, with > 99 % radiochemical purity and 41 - 282 GBq/μmol specific activity. Both tracers were highly hydrophilic with LogD7.4 of -2.65 ± 0.15 and -4.15 ± 0.04 for P05022 and Z02176, respectively. The PET imaging and biodistribution studies at 1-h post-injection showed extremely low background (~ 1 %ID/g or less) of both tracers. Only kidneys, bladder, and B1R+ tumor were clearly visualized in PET images. The biodistribution data showed that both tracers were excreted mainly via the renal pathway. At 1-h post-injection, B1R+ tumor uptake for 68Ga-Z02176 (28.9 ± 6.21 %ID/g) was higher than 68Ga-P05022 (11.6 ± 3.30 %ID/g). The B1R+ tumor-to-blood and B1R+ tumor-to-muscle ratios were also higher with 68Ga-Z02176 (56.1 ± 17.3 and 167 ± 57.6) compared to 68Ga-P05022 (34.3 ± 15.2 and 103 ± 30.2). Negligible uptake in B1R- tumors indicated that the uptake in B1R+ tumors was receptor mediated. In addition, co-injecting with the cold standard reduced B1R+ tumor uptake by more than 85 % for both radiotracers. Conclusions 68Ga-P05022, 68Ga-Z02176, and their cold compounds were successfully synthesized and characterized. Both tracers had high binding affinities for B1R. PET imaging and biodistribution studies revealed that 68Ga-Z02176 was superior to 68Ga-P05022 and other previously reported tracers for B1R-targeting imaging. Our results indicate that 68Ga-Z02176 warrants further studies for potential clinical translation.
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) | 0,001 | 0,000 |
| 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 | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».