A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging

Chang, Chi Wei; Lin, Min; Wu, Su Ying; Hsieh, Cheng-Hong; Liu, R. S.; Huang, Kuang Liang; Chen, C. H.; Wang, H. E.

doi:10.1016/j.apradiso.2006.06.005

Cited by 11 publications

(4 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, preparing 9-(4-[ 18 F]-fluoro-3-hydroxymethylbutyl)guanine by radiofluorination of its tosyl precursor in DMSO gave higher radiochemical yield than that in acetonitrile [23]. In this study, conducting nucleophilic 18 F-fluorination of compound 2 with K[ 18 F]/K2.2.2 in DMSO afforded noncarrier-added [ 18 F]FPBZA with high radiochemical yield.…”

Section: Discussionmentioning

confidence: 79%

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

Wu¹,

Huang

et al. 2014

BioMed Research International

View full text Add to dashboard Cite

Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81 ± 0.82 %ID/g), compared with A375 tumor and inflammation lesion (3.00 ± 0.71 and 1.67 ± 0.56 %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77 ± 0.36 %ID/g at 2 h (versus 1.16 ± 0.23 %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions.

show abstract

Section: Discussionmentioning

confidence: 79%

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

Wu¹,

Huang

et al. 2014

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…5 ). In order to evaluate the transduction efficiency of transgene at tumor site and monitor therapeutic value, we applied in vivo optical imaging and PET imaging using a radioactive thymidine kinase specific tracer, [ 18 F]FHBG 26 . Significant reduction of Fluc signal was observed 4 days after two doses of prodrug treatment in the mice infected with Lenti-STAT3-NF-κB-tk as compared with the mice infected with Lenti-CMV- tk or treated with the same amount of GCV and PBS alone.…”

Section: Discussionmentioning

confidence: 99%

“…[ 18 F]FHBG is one of the PET report probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-TK) and mutant HSV1-sr39tk report gene 25 . [ 18 F]FHBG was synthesized by nucleophilic method as described previously 26 . Imaging was performed using a microPET R4 scanner (CTI Concorde Microsystems, Knoxville, TN, USA), equipped with a small-animal PET Manager, (version 2.2.4; Concord Microsystems) for data acquisition and imaging process.One hour prior to imaging, mice were injected i.v.…”

Section: Methodsmentioning

confidence: 99%

STAT3/NF-κB-Regulated Lentiviral TK/GCV Suicide Gene Therapy for Cisplatin-Resistant Triple-Negative Breast Cancer

Kuo¹,

Hwu

et al. 2017

Theranostics

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs). In this study, we have cloned a novel STAT3/NF-κB-based reporter system to drive the expression of herpes simplex virus thymidine kinase (HSV-TK) against breast cancer. Lentiviral vector expressing HSV-TK under the regulation of STAT3/NF-κB fused response element was developed. In this setting, we exploited the constitutive STAT3/NF-κB activation in tumors to achieve higher transgene expression than that driven by a constitutively active CMV promotor in vivo. An orthotropic MDA-MB-231 triple negative breast cancer mouse model was used for evaluating the feasibility of STAT3-NF-κB-TK/GCV suicide gene therapy system.The basal promoter activity of Lenti-CMV-TK and Lenti-STAT3-NF-κB-TK in MDA-MB-231 cells was compared by 3H-FEAU uptake assay. The Lenti-CMV-TK showed ~5 fold higher 3H-FEAU uptake then Lenti -STAT3-NF-κB-TK. In clonogenic assay, cells expressing Lenti-CMV-TK were 2-fold more sensitive to GCV than Lenti-STAT3-NF-κB-TK transduced cells. In vitro effect of STAT3-NF-κB-induced transgene expression was determined by 10ng/mL TNF-α induction and confirmed by western blot analysis and DsRedm fluorescent microscopy. In vivo evaluation of therapeutic effect by bioluminescence and [18F]FHBG microPET imaging indicated that Lenti-STAT3-NF-κB-TK showed more tumor growth retardation than Lenti-CMV-TK when GCV (20 mg/kg) was administered. The invasiveness and expression of cancer stem cell markers were both decreased after STAT3/NF-κB-regulated HSV-TK/GCV therapy. Moreover, STAT3/NF-κB signaling targeting could further sensitize tumor cells to cisplatin. This study successfully established a theranositic approach to treat triple-negative breast cancer via STAT3-NF-κB responsive element-driven suicide gene therapy. This platform may also be an alternative strategy to handle with drug-resistant cancer cells.

show abstract

“…Synthesis was adapted from multiple literature sources with slight modifications ( 28–30 ). Tosyl-FHBG (4 mg in 1 mL MeCN, 4 mM) was added to the activated [ 18 F]fluoride residue in reaction vessel one, and the solution reacted at 135°C for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification

Lazari

Collins

Shen

et al. 2014

Journal of Nuclear Medicine Technology

View full text Add to dashboard Cite

Fully-automated radiosynthesizers are continuing to be developed to meet the growing need for the reliable production of positron emission tomography (PET) tracers made under current good manufacturing practice (cGMP) guidelines. There is a current trend towards supporting “kit-like” disposable cassettes that come preconfigured for particular tracers, thus eliminating the need for cleaning protocols between syntheses and enabling quick transitions to synthesizing other tracers. Though ideal for production, these systems are often limited for the development of novel tracers due to pressure, temperature, and chemical compatibility considerations. This study demonstrates the versatile use of the ELIXYS fully-automated radiosynthesizer to adapt and produce eight different 18F-labeled PET tracers of varying complexity. Methods Three reactor syntheses of D-[18F]FAC, L-[18F]FMAU, and D-[18F]FEAU along with the one reactor syntheses of D-[18F]FEAU, [18F]FDG, [18F]FLT, [18F]Fallypride, [18F]FHBG, and [18F]SFB were all produced using ELIXYS without the need for any hardware modifications or reconfiguration. Synthesis protocols were adapted, and slightly modified from literature, but not fully optimized. Furthermore, [18F]FLT, [18F]FDG, and [18F]Fallypride were produced sequentially on the same day and used for preclinical imaging of A431 tumor-bearing SCID mice and wild-type BALB/c mice, respectively. To assess future translation to the clinical setting, several batches of tracers were subjected to a full set of quality control tests. Results All tracers were produced with radiochemical yields comparable to those in literature. [18F]FLT, [18F]FDG, and [18F]Fallypride were successfully used to image the mice with results consistent with literature. All tracers subjected to clinical quality control tests passed. Conclusion The ELIXYS radiosynthesizer facilitates rapid tracer development and is capable of producing multiple 18F-labeled PET tracers suitable for clinical applications using the same hardware setup.

show abstract

A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging

Cited by 11 publications

References 15 publications

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

STAT3/NF-κB-Regulated Lentiviral TK/GCV Suicide Gene Therapy for Cisplatin-Resistant Triple-Negative Breast Cancer

Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification

Contact Info

Product

Resources

About

A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging

Cited by 11 publications

References 15 publications

Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma

Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma

STAT3/NF-κB-Regulated Lentiviral TK/GCV Suicide Gene Therapy for Cisplatin-Resistant Triple-Negative Breast Cancer

Fully Automated Production of Diverse 18F-Labeled PET Tracers on the ELIXYS Multireactor Radiosynthesizer Without Hardware Modification

Contact Info

Product

Resources

About

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma

Synthesis and Preclinical Characterization of [¹⁸F]FPBZA: A Novel PET Probe for Melanoma