Synthesis and Preliminary Evaluation of 9-(4-18FFluoro-3-hydroxymethylbutyl) Guanine (18FFHBG) in HSV1-tk Gene Transduced Hepatoma Cell / 핵의학분자영상
Nuclear Medicine and Molecular Imaging
;
: 218-227, 2006.
Artigo
em Coreano
| WPRIM
| ID: wpr-191180
ABSTRACT
PURPOSE:
The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. MATERIALS ANDMETHODS:
Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[18F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [18F]FHBG were performed, and was analyzed correlation between [18F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model.RESULTS:
[18F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 GBq/micro mol. Specific accumulation of [18F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [18F]FHBG was retained inside of cells. The uptake of [18F]FHBG was showed a highly significant linear correlation (R2=0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors.CONCLUSION:
[18F]FHBG appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Suicídio
/
Timidina Quinase
/
Terapia Genética
/
Expressão Gênica
/
Contagem de Células
/
Genes Reporter
/
Carcinoma Hepatocelular
/
Guanina
Limite:
Animais
Idioma:
Coreano
Revista:
Nuclear Medicine and Molecular Imaging
Ano de publicação:
2006
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS