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Microwave-assisted One-pot Synthesis of N-succinimidyl-4-[18F]fluorobenzoate [18F]SFB
Published on: June 28, 2011
Development of a novel 18F-labeled small molecule probe for PET imaging of mesenchymal epithelial transition receptor
Lihong Bu1,2, Xiaowei Ma3, Aiyan Ji4,5
1PET-CT/MRI Center, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Abstract:
The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternative tool for visualizing whole-body c-Met expression quantitatively and noninvasively. Here we firstly reported an 18F labeled, small-molecule quinine compound-based PET probe, 1-(4-(5-amino-7-(trifluoromethyl) quinolin-3-yl) piperazin-1-yl)-2-(fluoro-[18F]) propan-1-one, herein referred as [18F]-AZC.
Methods:
[18F]-AZC was synthesized via a one-step substitution reaction and characterized by radiochemistry methods. [18F]-AZC specificity and affinity toward c-Met were assessed by cell uptake assay, with or without cold compound [19F]-AZC or commercial c-Met inhibitor blocking. MicroPET/CT imaging and biodistribution studies were conducted in subcutaneous murine xenografts of glioma. Additionally, [18F]-AZC was then further evaluated in orthotopic glioma xenografts, by microPET/CT imaging accompanied with MRI and autoradiography for co-registration of the tumor. Immunofluorescence staining was also carried out to qualitatively evaluate the c-Met expression in tumor tissue, co-localizes with H&E staining.
Results:
This probe shows easy radiosynthesis, high stability in vitro and in vivo, high targeting affinity, and favorable lipophilicity and brain transport coefficient. [18F]-AZC demonstrates excellent tumor imaging properties in vivo and can delineate c-Met positive glioma specifically at 1 h after intravenous injection of the probe. Moreover, favorable correlation was observed between the [18F]-AZC accumulation and the amount of c-Met expression in tumor.
Conclusion:
This novel imaging probe could be applied as a valuable tool for management of anti-c-Met therapies in patients in the future.
Insights
A new PET probe, [18F]-AZC, allows noninvasive visualization of c-Met expression in tumors. This tool can help manage anti-c-Met therapies by overcoming tumor heterogeneity challenges.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- The mesenchymal epithelial transition factor (c-Met) is a validated anticancer target, but its expression heterogeneity complicates anti-c-Met therapies.
- There is a need for noninvasive tools to quantitatively assess whole-body c-Met expression.
Purpose of the Study:
- To develop and evaluate a novel 18F-labeled PET probe, [18F]-AZC, for visualizing c-Met expression.
- To assess the probe's efficacy in preclinical glioma models.
Main Methods:
- [18F]-AZC was synthesized and characterized. Specificity and affinity were confirmed via cell uptake assays.
- MicroPET/CT imaging and biodistribution studies were performed in subcutaneous and orthotopic glioma xenografts.
- Co-registration with MRI and autoradiography, along with immunofluorescence staining, were used for validation.
Main Results:
- [18F]-AZC demonstrated easy radiosynthesis, high in vitro/in vivo stability, and favorable physicochemical properties including brain transport.
- The probe effectively delineated c-Met-positive gliomas with high specificity at 1 hour post-injection.
- A positive correlation was found between [18F]-AZC accumulation and c-Met expression levels in tumors.
Conclusions:
- [18F]-AZC is a promising PET imaging probe for c-Met.
- This novel probe has the potential to aid in the management of anti-c-Met therapies for cancer patients.
