Improved Radiosynthesis and Biological Evaluations of L- and D-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of IDO-Mediated Kynurenine Pathway of Tryptophan Metabolism.
Purpose: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (...
| Publicado en: | Molecular Imaging & Biology Vol. 19; no. 4; pp. 589 - 599 |
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| Autores principales: | , |
| Formato: | diagnostic images pictorial research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=123926961&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 123926961 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15361632 KJU jtl: Molecular Imaging & Biology issn: 15361632 maglogo: N pubinfo: dt: Aug2017 vid: 19 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 123926961 123926961 143985997 NLM27815661 123926961 10.1007/s11307-016-1024-z NLM27815661 123926961 ppf: 589 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Improved Radiosynthesis and Biological Evaluations of L- and D-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of IDO-Mediated Kynurenine Pathway of Tryptophan Metabolism. aug: au: Xin, Yangchun Cai, Hancheng affil: Department of Radiology , University of Texas Southwestern Medical Center , Dallas 75390 USA sug: subj: Tomography, Emission-Computed Tryptophan Metabolism Oxidoreductases Metabolism Fluorine Radioisotopes Amino Acids Metabolism Mice Cell Line, Tumor Animal Studies Tryptophan Quality Control (Technology) ab: Purpose: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (PET) could provide valuable information for noninvasive assessment of cancer immunotherapy response. In this work, radiotracer 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) and its enantioisomer 1-D-[18F]FETrp were synthesized and evaluated for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism.Procedures: Enantiopure 1-L-[18F]FETrp and 1-D-[18F]FETrp were prepared by a nucleophilic reaction of N-boc-1-(2-tosylethyl) tryptophan tert-butyl ester with [18F]Fluoride, followed by acid hydrolysis in a GE Tracerlab FX-N module. In vitro cell uptake assays were performed with a breast cancer cell line MDA-MB-231. Small animal PET/computed tomography (CT) imaging was carried out in a mouse model bearing MDA-MB-231 xenografts.Results: Automatic radiosynthesis of 1-L-[18F]FETrp and 1-D-[18F]FETrp was achieved by a one-pot two-step approach in 19.0 ± 7.0 and 9.0 ± 3.0 % (n = 3) decay-corrected yield with radiochemical purity over 99 %, respectively. In vitro cell uptake study indicated the uptake of 1-D-[18F]FETrp in MDA-MB-231 cells was 0.73 ± 0.07 %/mg of protein at 60 min, while, the corresponding uptake of 1-L-[18F]FETrp was 6.60 ± 0.77 %/mg. Further mechanistic assays revealed that amino acid transport systems L-tpye amino acid transporter (LAT) and alanine-, serine-, and cysteine-preferring (ASC), and enzyme IDO expression were involved in cell uptake of 1-L-[18F]FETrp. Small animal PET/CT imaging study showed the tumor uptake of 1-L-[18F]FETrp was 4.6 ± 0.4 % ID/g, while, the tumor uptake of 1-D-[18F]FETrp was low to 1.0 ± 0.2 % ID/g, which were confirmed by ex vivo biodistribution study.Conclusions: We have developed a practical method for the automatic radiosynthesis of 1-L-[18F]FETrp and 1-D-[18F]FETrp. Our biological evaluation results suggest that 1-L-[18F]FETrp is a promising radiotracer for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism in cancer. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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