Abstract:
:Similar to glycolysis, glutaminolysis acts as a vital energy source in tumor cells, providing building blocks for the metabolic needs of tumor cells. To capture glutaminolysis in tumors, 18F-(2S,4R)4-fluoroglutamine ([18F]FGln) and 18F-fluoroboronoglutamine ([18F]FBQ) have been successfully developed for positron emission tomography (PET) imaging, but these two molecules lack stability, resulting in undesired yet significant bone uptake. In this study, we found that [18F]FBQ-C2 is a stable Gln PET tracer by adding two more methylene groups to the side chain of [18F]FBQ. [18F]FBQ-C2 was synthesized with a good radiochemical yield of 35% and over 98% radiochemical purity. [18F]FBQ-C2 showed extreme stability in vitro, and no defluorination was observed after 2 h in phosphate buffered saline at 37 °C. The competitive inhibition assay results indicated that [18F]FBQ-C2 enters cells via the system ASC and N, similar to natural glutamine, and can be transported by tumor-overexpressed ASCT2. PET imaging and biodistribution results indicated that [18F]FBQ-C2 is stable in vivo with low bone uptake (0.81 ± 0.20% ID/g) and can be cleared rapidly from most tissues. Dynamic scan and pharmacokinetic studies using BGC823-xenograft-bearing mice revealed that [18F]FBQ-C2 accumulates specifically in tumors, with a longer half-life (101.18 ± 6.50 min) in tumor tissues than in other tissues (52.70 ± 12.44 min in muscle). Biodistribution exhibits a high tumor-to-normal tissue ratio (4.8 ± 1.7 for the muscle, 2.5 ± 1.0 for the stomach, 2.2 ± 0.9 for the liver, and 17.8 ± 8.4 for the brain). In conclusion, [18F]FBQ-C2 can be used to perform high-contrast Gln imaging of tumors and can serve as a PET tracer for clinical research.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Chen J,Li C,Hong H,Liu H,Wang C,Xu M,Han Y,Liu Zdoi
10.1021/acs.molpharmaceut.9b00891subject
Has Abstractpub_date
2019-12-02 00:00:00pages
5035-5041issue
12eissn
1543-8384issn
1543-8392journal_volume
16pub_type
杂志文章abstract::It is well established that polymers adopt a range of conformations and solution-state organization in response to varying solution environments, although very little work has been done to understand how these effects might impact the physical stability and bioavailability of spray-dried amorphous dispersions (SDDs). ...
journal_title:Molecular pharmaceutics
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pub_type: 临床试验,杂志文章
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