9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG)의 합성과 헤르페스 단순 바이러스 티미딘 키나아제 이입 간암 세포주에서의 기초 연구 (Synthesis and Preliminary Evaluation of 9-(4-[18F]Fluoro-3-hydroxymethylbutyl) Guanine ([18F]FHBG) in HSV1-tk Gene Transduced Hepatoma Cell) |
Author |
문병석1,이태섭2,이명근4,이교철1,안광일1,전권수1,오옥두4,지대윤5,최창운2,3,임상무2,3,천기정1,2,3, |
Byung Seok Moon,M.S.1, Tae Sup Lee, Ph.D.2, Myoung Keun Lee, M.S.4,Kyo Chul Lee, Ph.D.1,Gwang Il An, Ph.D.1, Kwon Soo Chun, Ph.D.1, Ok Doo Awh, Ph.D.4, Dae Yoon Chi, Ph.D.5,Chang Woon Choi, M.D. & Ph.D.2,3, Sang Moo Lim, M.D. & Ph.D.2,3, and Gi Jeong Cheo |
Affiliation |
원자력의학원 RI 및 방사성의약품개발실1, 핵의학연구실2, 핵의학과3, 연세대학교 임상병리학과4,인하대학교 화학과5 1Laboratory of Radiopharmaceuticals, 2Laboratory of Nuclear Medicine, 3Department of Nuclear Medicine, Korea, Institute of Radiological and Medical Sciences, Seoul, Korea; 4Department of Medical Laboratory Science, Yonsei University, Wonju, Korea; 5Depart |
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 and Methods: 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/μmol. 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. (Nucl Med
Mol Imaging 2006;40(4):218-227) |
Keyword |
[18F]FHBG, thymidine kinase, gene therapy, PET |
Full text Article |
4004218.pdf
|
|
|