Synthesis and Preclinical Evaluation of 18F-PEG3-FPN for the Detection of Metastatic Pigmented Melanoma.
Mol Pharm
; 14(11): 3896-3905, 2017 11 06.
Article
em En
| MEDLINE
| ID: mdl-29037039
ABSTRACT
Although 18F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (18F-5-FPN) is considered a promising radiopharmaceutical for PET imaging of melanoma, it accumulates at high concentrations in the liver. The aim in this research was to optimize the structure of 18F-5-FPN with triethylene glycol to reduce liver uptake as well as improve pharmacokinetics, and to evaluate its performance in detection of melanoma liver and lung metastases. 18F-PEG3-FPN was successfully prepared with a high radiolabeling yield (44.68% ± 5.99%) and radiochemical purity (>99%). The uptake of 18F-PEG3-FPN by pigmented B16F10 melanoma cells was significantly higher than that by amelanotic melanoma A375 cells. The binding to B16F10 cells could be blocked by excess 19F-PEG3-FPN. On small animal PET images, B16F10 tumors, but not A375 tumors, were clearly delineated after 18F-PEG3-FPN injection. More importantly, 18F-PEG3-FPN uptake by liver (2.27 ± 0.45 and 1.74 ± 0.35% ID/g, at 1 and 2 h) was significantly lower than that of 18F-5-FPN, and the lesions in lung and liver could be clearly detected by 18F-PEG3-FPN PET imaging in mouse models of pulmonary or hepatic metastases. Overall, we successfully synthesized 18F-PEG3-FPN, which has higher labeling efficacy and better in vivo pharmacokinetics along with lower liver uptake compared to 18F-5-FPN. This suggests 18F-PEG3-FPN as a candidate for pigmented melanoma liver and lung metastasis detection.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ácidos Picolínicos
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Benzamidas
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Fluordesoxiglucose F18
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Tomografia por Emissão de Pósitrons
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Melanoma
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Pharm
Assunto da revista:
BIOLOGIA MOLECULAR
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FARMACIA
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FARMACOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China