Comparison of Amino Acid Positron Emission Tomographic Radiotracers for Molecular Imaging of Primary and Metastatic Brain Tumors

Overview

Journal Mol Imaging

Publisher Sage Publications

Specialty Radiology

Date 2014 May 15

PMID 24825818

Citations 56

Authors

Csaba Juhasz

Shalini Dwivedi

David O Kamson

Sharon K Michelhaugh

Sandeep Mittal

Affiliations

Soon will be listed here.

Abstract

Positron emission tomography (PET) is an imaging technology that can detect and characterize tumors based on their molecular and biochemical properties, such as altered glucose, nucleoside, or amino acid metabolism. PET plays a significant role in the diagnosis, prognostication, and treatment of various cancers, including brain tumors. In this article, we compare uptake mechanisms and the clinical performance of the amino acid PET radiotracers (l-[methyl-11C]methionine [MET], 18F-fluoroethyl-tyrosine [FET], 18F-fluoro-l-dihydroxy-phenylalanine [FDOPA], and 11C-alpha-methyl-l-tryptophan [AMT]) most commonly used for brain tumor imaging. First, we discuss and compare the mechanisms of tumoral transport and accumulation, the basis of differential performance of these radioligands in clinical studies. Then we summarize studies that provided direct comparisons among these amino acid tracers and to clinically used 2-deoxy-2[18F]fluoro-d-glucose [FDG] PET imaging. We also discuss how tracer kinetic analysis can enhance the clinical information obtained from amino acid PET images. We discuss both similarities and differences in potential clinical value for each radioligand. This comparative review can guide which radiotracer to favor in future clinical trials aimed at defining the role of these molecular imaging modalities in the clinical management of brain tumor patients.

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References

Dhermain F, Hau P, Lanfermann H, Jacobs A, van den Bent M . Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 2010; 9(9):906-20. DOI: 10.1016/S1474-4422(10)70181-2. View

Nioche C, Soret M, Gontier E, Lahutte M, Dutertre G, Dulou R . Evaluation of quantitative criteria for glioma grading with static and dynamic 18F-FDopa PET/CT. Clin Nucl Med. 2013; 38(2):81-7. DOI: 10.1097/RLU.0b013e318279fd5a. View

Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H . O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med. 2011; 52(6):856-64. DOI: 10.2967/jnumed.110.086645. View

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

Youland R, Kitange G, Peterson T, Pafundi D, Ramiscal J, Pokorny J . The role of LAT1 in (18)F-DOPA uptake in malignant gliomas. J Neurooncol. 2012; 111(1):11-8. PMC: 3907171. DOI: 10.1007/s11060-012-0986-1. View

Washburn L, Sun T, Byrd B, Hayes R, Butler T . DL-[Carboxyl-11C]tryptophan, a potential agent for pancreatic imaging; production and preclinical investigations. J Nucl Med. 1979; 20(8):857-64. View

Juhasz C, Chugani D, Padhye U, Muzik O, Shah A, Asano E . Evaluation with alpha-[11C]methyl-L-tryptophan positron emission tomography for reoperation after failed epilepsy surgery. Epilepsia. 2004; 45(2):124-30. DOI: 10.1111/j.0013-9580.2004.30303.x. View

Kuhnt D, Bauer M, Ganslandt O, Nimsky C . Functional imaging: where do we go from here?. J Neurosurg Sci. 2013; 57(1):1-11. View

Diksic M, Nagahiro S, Chaly T, Sourkes T, YAMAMOTO Y, FEINDEL W . Serotonin synthesis rate measured in living dog brain by positron emission tomography. J Neurochem. 1991; 56(1):153-62. DOI: 10.1111/j.1471-4159.1991.tb02575.x. View

10.

Juhasz C, Nahleh Z, Zitron I, Chugani D, Janabi M, Bandyopadhyay S . Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies. Nucl Med Biol. 2012; 39(7):926-32. PMC: 3443322. DOI: 10.1016/j.nucmedbio.2012.01.010. View

11.

Christensen M, Kamson D, Snyder M, Kim H, Robinette N, Mittal S . Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients. J Radiat Oncol. 2014; 3(2):131-138. PMC: 4235785. DOI: 10.1007/s13566-013-0132-5. View

12.

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

13.

Stockhammer F, Plotkin M, Amthauer H, van Landeghem F, Woiciechowsky C . Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in non-contrast-enhancing gliomas. J Neurooncol. 2008; 88(2):205-10. DOI: 10.1007/s11060-008-9551-3. View

14.

Alkonyi B, Mittal S, Zitron I, Chugani D, Kupsky W, Muzik O . Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors. J Neurooncol. 2011; 107(2):365-72. PMC: 3296904. DOI: 10.1007/s11060-011-0750-y. View

15.

Salber D, Stoffels G, Pauleit D, Oros-Peusquens A, Shah N, Klauth P . Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses. J Nucl Med. 2007; 48(12):2056-62. DOI: 10.2967/jnumed.107.046615. View

16.

Munn D, Mellor A . Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest. 2007; 117(5):1147-54. PMC: 1857253. DOI: 10.1172/JCI31178. View

17.

Mitsuka K, Kawataki T, Satoh E, Asahara T, Horikoshi T, Kinouchi H . Expression of indoleamine 2,3-dioxygenase and correlation with pathological malignancy in gliomas. Neurosurgery. 2013; 72(6):1031-8. DOI: 10.1227/NEU.0b013e31828cf945. View

18.

Muzik O, Chugani D, Chakraborty P, Mangner T, Chugani H . Analysis of [C-11]alpha-methyl-tryptophan kinetics for the estimation of serotonin synthesis rate in vivo. J Cereb Blood Flow Metab. 1997; 17(6):659-69. DOI: 10.1097/00004647-199706000-00007. View

19.

Popperl G, Kreth F, Herms J, Koch W, Mehrkens J, Gildehaus F . Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods?. J Nucl Med. 2006; 47(3):393-403. View

20.

Chugani D, Muzik O . Alpha[C-11]methyl-L-tryptophan PET maps brain serotonin synthesis and kynurenine pathway metabolism. J Cereb Blood Flow Metab. 2000; 20(1):2-9. DOI: 10.1097/00004647-200001000-00002. View