Synthesis and Initial Evaluation of Radioactive 5-I-α-methyl-tryptophan: a Trp Based Agent Targeting IDO-1

Overview

Journal Medchemcomm

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2019 Jun 14

PMID 31191872

Citations 1

Authors

Benjamin C Giglio

Hui Wang

Xuefeng Yan

Zibo Li

Affiliations

Soon will be listed here.

Abstract

A synthetic approach is established to achieve radioactive 5-I-α-methyl-tryptophan (5-I-AMT). An enzyme based assay demonstrated that 5-I-AMT is a substrate of IDO-1. The distribution and imaging potential of 5-I-AMT were explored with a B16F10 tumor model using I-124 as the radiotag.

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References

Kamson D, Mittal S, Robinette N, Muzik O, Kupsky W, Barger G . Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma. Neuro Oncol. 2014; 16(10):1373-83. PMC: 4165412. DOI: 10.1093/neuonc/nou042. View

Diksic M, Tohyama Y, Takada A . Brain net unidirectional uptake of alpha-[14c]methyl-L-tryptophan (alpha-MTrp) and its correlation with regional serotonin synthesis, tryptophan incorporation into proteins, and permeability surface area products of tryptophan and alpha-MTrp. Neurochem Res. 2001; 25(12):1537-46. DOI: 10.1023/a:1026654116999. View

Kai S, Goto S, Tahara K, Sasaki A, Tone S, Kitano S . Indoleamine 2,3-dioxygenase is necessary for cytolytic activity of natural killer cells. Scand J Immunol. 2004; 59(2):177-82. DOI: 10.1111/j.0300-9475.2004.01378.x. View

Beatty G, ODwyer P, Clark J, Shi J, Bowman K, Scherle P . First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies. Clin Cancer Res. 2017; 23(13):3269-3276. PMC: 5496788. DOI: 10.1158/1078-0432.CCR-16-2272. View

Patton J, Bennuru S, Eberhard M, Hess J, Torigian A, Lustigman S . Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum. PLoS Negl Trop Dis. 2018; 12(12):e0006977. PMC: 6306240. DOI: 10.1371/journal.pntd.0006977. View

Lena I, Ombetta J, Chalon S, Dognon A, Baulieu J, Frangin Y . Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT. Nucl Med Biol. 1995; 22(6):727-36. DOI: 10.1016/0969-8051(95)00019-t. View

Fu R, Zhang Y, Li H, Lv W, Zhao L, Guo Q . LW106, a novel indoleamine 2,3-dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma-immune crosstalk and cancer stem cell enrichment in tumour micro-environment. Br J Pharmacol. 2018; 175(14):3034-3049. PMC: 6016675. DOI: 10.1111/bph.14351. View

Davar D, Bahary N . Modulating Tumor Immunology by Inhibiting Indoleamine 2,3-Dioxygenase (IDO): Recent Developments and First Clinical Experiences. Target Oncol. 2018; 13(2):125-140. DOI: 10.1007/s11523-017-0547-9. View

Giglio B, Fei H, Wang M, Wang H, He L, Feng H . Synthesis of 5-[F]Fluoro-α-methyl Tryptophan: New Trp Based PET Agents. Theranostics. 2017; 7(6):1524-1530. PMC: 5436511. DOI: 10.7150/thno.19371. View

10.

Diksic M, Young S . Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem. 2001; 78(6):1185-200. DOI: 10.1046/j.1471-4159.2001.00536.x. View

11.

Bosnyak E, Kamson D, Guastella A, Varadarajan K, Robinette N, Kupsky W . Molecular imaging correlates of tryptophan metabolism via the kynurenine pathway in human meningiomas. Neuro Oncol. 2015; 17(9):1284-92. PMC: 4588760. DOI: 10.1093/neuonc/nov098. View

12.

Prendergast G, Malachowski W, Mondal A, Scherle P, Muller A . Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer. Int Rev Cell Mol Biol. 2018; 336:175-203. PMC: 6054468. DOI: 10.1016/bs.ircmb.2017.07.004. View

13.

Waghorn P, Jackson M, Gouverneur V, Vallis K . Targeting telomerase with radiolabeled inhibitors. Eur J Med Chem. 2016; 125:117-129. PMC: 5154340. DOI: 10.1016/j.ejmech.2016.09.028. View

14.

Juhasz C, Dwivedi S, Kamson D, Michelhaugh S, Mittal S . Comparison of amino acid positron emission tomographic radiotracers for molecular imaging of primary and metastatic brain tumors. Mol Imaging. 2014; 13. PMC: 4199087. DOI: 10.2310/7290.2014.00015. View

15.

Robert C, Schachter J, Long G, Arance A, Grob J, Mortier L . Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015; 372(26):2521-32. DOI: 10.1056/NEJMoa1503093. View