Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET.
Mol Imaging Biol
; 20(5): 798-807, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-29464496
ABSTRACT
PURPOSE:
The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). PROCEDURES The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [68Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [68Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent.RESULTS:
The affinity of [68Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [68Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection.CONCLUSIONS:
Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ácido N-Acetilneuramínico
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Tomografía de Emisión de Positrones
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Imagen Molecular
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Radioisótopos de Galio
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Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Mol Imaging Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
Año:
2018
Tipo del documento:
Article
País de afiliación:
Grecia