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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 6/2019

01-12-2019 | Prostate Cancer | Research Article

Evaluation of l-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer

Authors: Yangchun Xin, Xiaofei Gao, Li Liu, Woo-Ping Ge, Manoj K. Jain, Hancheng Cai

Published in: Molecular Imaging and Biology | Issue 6/2019

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Abstract

Purpose

Fluorine-18 labeled tryptophan analog l-1-[18F]fluoroethyl-tryptophan (l-1-[18F]FETrp) was designed for positron emission tomography (PET) imaging of cancer by dual targeting of the overexpressed amino acid transporters and altered indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway of tryptophan metabolism. In our previous study, we described the radiosynthesis and preliminary evaluation of l-1-[18F]FETrp for PET imaging of breast cancer. The aim of this study was to investigate the in vivo imaging mechanism and further evaluate this radiotracer in more wide range types of cancers including prostate cancer, lung cancer, and glioma.

Procedures

The mice bearing subcutaneous PC-3 prostate cancer, subcutaneous H2009 and H460 lung cancers, subcutaneous MDA-MB-231, orthotopic A549 lung cancer, and intracranial 73C glioma were employed to evaluate l-1-[18F]FETrp for PET imaging of cancer. The in vivo catabolism of l-1-[18F]FETrp in the tumor was studied by analysis of PC-3 extracts with radio-HPLC.

Results

Small animal PET/CT imaging of l-1-[18F]FETrp visualized all tumors in these different mouse models with high accumulations of radioactivity in PC-3 (7.5 ± 0.6 % ID/g), H2009 (5.3 ± 0.8 % ID/g), H460 (9.0 ± 1.4 % ID/g), A549 (4.5 ± 0.5 % ID/g), and 73C (4.1 ± 0.7 % ID/g) tumors. The radio-HPLC analysis of PC-3 tumor extracts revealed that about 30 % of l-1-[18F]FETrp was converted into a highly polar radioactive metabolite. The uptake in H460 cancer was about 1.7-fold higher than that in H2009 cancer, which indicated l-1-[18F]FETrp could differentiate these subtypes of lung cancers (H2009 and H460) by imaging quantification. Furthermore, small animal PET/CT imaging in intracranial glioma revealed l-1-[18F]FETrp could pass blood-brain barrier (BBB) and accumulate in glioma with a favorable imaging contrast (tumor-to-brain 2.9).

Conclusions

l-1-[18F]FETrp highly accumulated in a wide range of malignancies including lung cancer, prostate cancer, and glioma. These results suggested that l-1-[18F]FETrp is a promising radiotracer for PET imaging of cancer.
Appendix
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Literature
1.
Vécsei L, Szalárdy L, Fülöp F, Toldi J (2013) Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov 12:64–82CrossRefPubMed
2.
Dounay AB, Tuttle JB, Verhoest PR (2015) Challenges and opportunities in the discovery of new therapeutics targeting the kynurenine pathway. J Med Chem 58:8762–8782CrossRefPubMed
3.
4.
Karanikas V, Zamanakou M, Kerenidi T, Dahabreh J, Hevas A, Nakou M, Gourgoulianis KI, Germenis AE (2007) Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer. Cancer Biol Ther 6:1258–1262CrossRefPubMed
5.
Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, Boon T, van den Eynde BJ (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274CrossRefPubMed
6.
Astigiano S, Morandi B, Costa R, Mastracci L, D'Agostino A, Ratto GB, Melioli G, Frumento G (2005) Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 7:390–396CrossRefPubMedPubMedCentral
7.
8.
Brochez L, Chevolet I, Kruse V (2017) The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy. Eur J Cancer 76:167–182CrossRefPubMed
9.
Perez RP, Riese MJ, Lewis KD, Saleh MN, Adil Daud JB (2017) Epacadostat plus nivolumab in patients with advanced solid tumors: preliminary phase I/II results of ECHO-204 [ASCO abstract 3003]. J Clin Oncol 35:3003–3003CrossRef
10.
Zakharia Y, McWilliams R, Shaheen M, Grossman K, Drabick J, Milhem M, Rixie O, Khleif S, Lott R, Kennedy E, David Munn NV, CL (2017) Interim analysis of the phase 2 clinical trial of the IDO pathway inhibitor indoximod in combination with pembrolizumab for patients with advanced melanoma. [AACR abstract CT117]. Cancer Res 77(13 Suppl):AM2017–ACT117
11.
Platten M, von Knebel Doeberitz N, Oezen I et al (2015) Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front Immunol 5:1–7CrossRef
12.
Godin-Ethier J, Hanafi LA, Piccirillo CA, Lapointe R (2011) Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. Clin Cancer Res 17:6985–6991CrossRefPubMed
13.
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMed
14.
Juhász C, Muzik O, Lu X et al (2009) Quantification of tryptophan transport and metabolism in lung tumors using PET. J Nucl Med 50:356–363CrossRefPubMed
15.
Huang X, Xiao X, Gillies RJ, Tian H (2016) Design and automated production of 11C-alpha-methyl-l-tryptophan (11C-AMT). Nucl Med Biol 43:303–308CrossRefPubMed
16.
Xin Y, Cai H (2017) Improved radiosynthesis and biological evaluations of L- and D-1-[18F]fluoroethyl-tryptophan for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism. Mol Imaging Biol 19:589–598CrossRefPubMed
17.
Michelhaugh SK, Muzik O, Guastella AR, Klinger NV, Polin LA, Cai H, Xin Y, Mangner TJ, Zhang S, Juhász C, Mittal S (2017) Assessment of tryptophan uptake and kinetics using 1-(2- 18 F-fluoroethyl)-l-tryptophan and α- 11 C-methyl-l-tryptophan PET imaging in mice implanted with patient-derived brain tumor xenografts. J Nucl Med 58:208–213CrossRefPubMedPubMedCentral
18.
Henrottin J, Lemaire C, Egrise D, Zervosen A, Van den Eynde B, Plenevaux A, Franci X, Goldman S, Andr’Luxen E, Luxen A, Jean Henrottin CL et al (2016) Fully automated radiosynthesis of 1-[18F]FETrp, a potential substrate for indoleamine 2,3-dioxygenase PET imaging. Nucl Med Biol 43:379–389CrossRefPubMed
19.
Sun T, Tang G, Tian H, Wang X, Chen X, Chen Z, Wang SC (2012) Radiosynthesis of 1-[18F]fluoroethyl-L-tryptophan as a novel potential amino acid PET tracer. Appl Radiat Isot 70:676–680CrossRefPubMed
20.
Kramer SD, Mu L, Muller A, Keller C, Kuznetsova OF, Schweinsberg C, Franck D, Muller C, Ross TL, Schibli R, Ametamey SM (2012) 5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET. J Nucl Med 53:434–442CrossRefPubMed
21.
Chiotellis A, Mu A, Ro SL et al (2016) Synthesis, radiolabeling, and biological evaluation of 5-hydroxy- 2-[18F]fluoroalkyl-tryptophan analogues as potential PET radiotracers for tumor imaging. J Med Chem 59:5324–5340CrossRefPubMed
22.
Zlatopolskiy BD, Zischler J, Urusova EA et al (2018) Discovery of 7-[18 F]fluorotryptophan as a novel positron emission tomography (PET) probe for the visualization of tryptophan metabolism in vivo. J Med Chem 61:189–206CrossRefPubMed
23.
Henrottin J, Zervosen A, Lemaire C, Sapunaric F, Laurent S, van den Eynde B, Goldman S, Plenevaux A, Luxen A (2015) N1-fluoroalkyltryptophan analogues: synthesis and in vitro study as potential substrates for indoleamine 2,3-dioxygenase. ACS Med Chem Lett 6:260–265CrossRefPubMedPubMedCentral
24.
Park GM, Lee S-M, Yim J-J, Yang S-C, Yoo CG, Lee C-T, Han SK, Young-Soo Shim YWK (2009) Expression of COX-2 and IDO by uteroglobin transduction in NSCLC cell lines transduction in NSCLC cell lines. Tuberc Respir Dis (Seoul) 66:274–279CrossRef
25.
Kudo Y, Boyd CAR (2000) Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection. Biochim Biophys Acta - Mol Basis Dis 1500:119–124CrossRef
26.
Bach-Gansmo T, Nanni C, Nieh PT, Zanoni L, Bogsrud TV, Sletten H, Korsan KA, Kieboom J, Tade FI, Odewole O, Chau A, Ward P, Goodman MM, Fanti S, Schuster DM, Willoch F (2017) Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine (18F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate Cancer. J Urol 197:676–683CrossRefPubMed
27.
Jha GG, Gupta S, Tagawa ST, Koopmeiners JS, Vivek S, Dudek AZ, Cooley SA, Blazar BR, JSM (2017) A phase II randomized, double-blind study of sipuleucel-T followed by IDO pathway inhibitor, indoximod, or placebo in the treatment of patients with metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol 35:3066–3066CrossRef
28.
29.
Wang Q, Holst J (2015) L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia. Am J Cancer Res 5:1281–1294PubMedPubMedCentral
30.
Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol 15:254–266CrossRefPubMed
Metadata
Title
Evaluation of l-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer
Authors
Yangchun Xin
Xiaofei Gao
Li Liu
Woo-Ping Ge
Manoj K. Jain
Hancheng Cai
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 6/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-019-01327-4

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