Noninvasive PET Imaging of a Ga-68-Radiolabeled RRL-Derived Peptide in Hepatocarcinoma Murine Models.
Mol Imaging Biol
; 21(2): 286-296, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-29916116
ABSTRACT
PURPOSE:
Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent. PROCEDURES RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68. Labeling yield was optimized by varying pH, temperature, and reaction time and the stability was evaluated in human fresh serum. Cellular uptakes of [68Ga]DOTA-RRL and FITC-conjugated RRL in HepG2 cells were evaluated using a gamma counter, confocal microscopy, and flow cytometry. PET images and biodistribution were performed in HepG2 tumor-bearing mice after injection of [68Ga]DOTA-RRL or [68Ga]GaCl3 at different time points. Further, blocking study was investigated using cold RRL.RESULTS:
The labeling yield of [68Ga]DOTA-RRL was 80.6 ± 3.9 % with a pH of 3.5-4.5 at 100 °C for 15 min. The cellular uptake of [68Ga]DOTA-RRL in HepG2 cells was significantly higher than that of [68Ga]GaCl3 (P < 0.05). Moreover, the high fluorescent affinity of FITC-conjugated RRL in HepG2 cells was shown using confocal microscopy and flow cytometry. After injection of [68Ga]DOTA-RRL in HepG2 tumor-bearing mice, tumor regions exhibited high radioactive accumulation over 120 min and the highest uptake at 30 min. After blocked with cold RRL, HepG2 tumors could not be visualized. [68Ga]GaCl3 was unable to show tumor images at any time point. The biodistribution results confirmed the PET imaging and blocking results.CONCLUSIONS:
Our study successfully prepared [68Ga]DOTA-RRL with a high labeling yield under the optimized reaction conditions and demonstrated its potential role as a PET imaging agent for tumor-targeted diagnosis.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Carcinoma Hepatocelular
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Tomografia por Emissão de Pósitrons
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Radioisótopos de Gálio
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Imaging Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China