• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.218-227
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• 2006

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), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) 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 $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(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 $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ 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: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ 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 $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) 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: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

• The Korean Journal of Nuclear Medicine Technology
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• v.15 no.2
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• pp.72-75
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• 2011

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage is that it is possible to monitor directly without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. This study was performed to automate 9-(4-[$^{18}F$] Fluoro-3-hydroxymethylbutyl) guanine ([$^{18}F$] FHBG) that are widely used as substrate for the HSV1-tk reporter gene in living organisms with positron emission tomography (PET) and find the optimized conditions of synthesis. Materials and Methods: Fully automated synthesis of [$^{18}F$] FHBG was performed using Explora-RN (CTI, USA) module. We have changed of reaction time (3, 5, 10 min) and temperature (110, 120, $130^{\circ}C$) for the optimized conditions of synthesis. Also we experimented to find the optimal concentration of precursor (5, 7, 10 mg). Results: [$^{18}F$] FHBG was purified by HPLC system and collected at around 10-12 min. Synthesis using Explora-RN module showed a $32.0{\pm}1.2%$ yield of radiochemical (decay corrected), the purity was greater than 98%. And the entire synthesis time was less than 48 min. Temperature of the highest synthesis yield was $130^{\circ}C$, reaction time was 5 minutes and concentration of precursor was 10 mg (recommended volume in manual) (n=36). In contrast to radiochemical yield of precursor 10 mg ($32{\pm}1.2%$), yield of 5 and 7 mg precursor was unstable. Conclusion: Automation of [$^{18}F$] FHBG synthesis at Explora-RN module has been completed. In addition, we were able to obtain optimized reaction time, temperature and concentration of precursor. Therefore this study would be provided more rapid synthesis and higher radiochemical yield.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.175-179
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• 2004

Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needic injection with or without catheter guidance. Tk expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.257-262
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• 2006

Purpose: The standard protocol using large volume of oral contrast media may cause gastrointestinal discomfort and contrast-related artifacts in PET/CT. The aim of this study was to evaluate the usefulness of low dose oral contrast in $^{18}F-FDG$ PET/CT. Materials and Methods: We retrospectively reviewed the whole-body PET/CT images in a total of 435 patients. About 200 ml of oval contrast agent (barium sulfate) was administered immediately before injection of $^{18}F-FDG$. The FDG uptake of intestines was analyzed by visual and semi- quantitative method on transaxial, coronal and saggital planes. Results: Seventy (16%, 113 sites) of 435 images showed high FDG uptake (peak SUV > 4); 50 (74%, 84 sites) with diffuse and 20 (15%, 29 sites) with focal uptake. The most commonly delivered site of oral contrast media was small bowel (n=27, 39%). On PET/CT images, FDG uptake coexisted with oral contrast media in 26 patients (54%, 38 sites) with diffuse pattern and 9 (45%, 9 sites) with focal pattern, and by sites, those were 38 (45%) and 9 (31%), respectively. In small bowel regions, the proportion of coexistence reached as high as 61% (29/47 sites). A visual analysis of available non-attenuation corrected PET images of 27 matched regions revealed no contrast-related artifact. Conclusion: We concluded that the application of low dose contrast media could be helpful in the evaluation of abdominal uptake in the FDG PET/CT image.