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Open Access 01-12-2018 | Original research

Discriminating radiation injury from recurrent tumor with [¹⁸F]PARPi and amino acid PET in mouse models

Authors: Patrick L. Donabedian, Susanne Kossatz, John A. Engelbach, Stephen A. Jannetti, Brandon Carney, Robert J. Young, Wolfgang A. Weber, Joel R. Garbow, Thomas Reiner

Published in: EJNMMI Research | Issue 1/2018

Abstract

Background

Radiation injury can be indistinguishable from recurrent tumor on standard imaging. Current protocols for this differential diagnosis require one or more follow-up imaging studies, long dynamic acquisitions, or complex image post-processing; despite much research, the inability to confidently distinguish between these two entities continues to pose a significant dilemma for the treating clinician. Using mouse models of both glioblastoma and radiation necrosis, we tested the potential of poly(ADP-ribose) polymerase (PARP)-targeted PET imaging with [¹⁸F]PARPi to better discriminate radiation injury from tumor.

Results

In mice with experimental radiation necrosis, lesion uptake on [¹⁸F]PARPi-PET was similar to contralateral uptake (1.02 ± 0.26 lesion/contralateral %IA/cc_max ratio), while [¹⁸F]FET-PET clearly delineated the contrast-enhancing region on MR (2.12 ± 0.16 lesion/contralateral %IA/cc_max ratio). In mice with focal intracranial U251 xenografts, tumor visualization on PARPi-PET was superior to FET-PET, and lesion-to-contralateral activity ratios (max/max, p = 0.034) were higher on PARPi-PET than on FET-PET.

Conclusions

A murine model of radiation necrosis does not demonstrate [¹⁸F]PARPi avidity, and [¹⁸F]PARPi-PET is better than [¹⁸F]FET-PET in distinguishing radiation injury from brain tumor. [¹⁸F]PARPi-PET can be used for discrimination between recurrent tumor and radiation injury within a single, static imaging session, which may be of value to resolve a common dilemma in neuro-oncology.

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Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY. Primary brain tumours in adults. Lancet. 2012;379:1984–96.CrossRefPubMed

Kohutek ZA, Yamada Y, Chan TA, Brennan CW, Tabar V, Gutin PH, et al. Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases. J Neuro-Oncol. 2015;125:149–56.CrossRef

Valk PE, Dillon WP. Radiation injury of the brain. Am J Neuroradiol. 1991;12:45–62.PubMed

Remler MP, Marcussen WH, Tiller-Borsich J. The late effects of radiation on the blood brain barrier. Int J Radiat Oncol Biol Phys. 1986;12:1965–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3771316.CrossRefPubMed

Walker AJ, Ruzevick J, Malayeri AA, Rigamonti D, Lim M, Redmond KJ, et al. Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression? Future Oncol. 2014;10:1277–97. Available from: http://www.futuremedicine.com/doi/10.2217/fon.13.271.CrossRefPubMedPubMedCentral

Kurita H, Kawahara N, Asai A, Ueki K, Shin M, Kirino T. Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. Neurol Res. 2001;23:869–74. Available from: http://www.tandfonline.com/doi/full/10.1179/016164101101199324.CrossRefPubMed

Yoshii Y. Pathological review of late cerebral radionecrosis. Brain Tumor Pathol. 2008;25:51–8.CrossRefPubMed

Enslow MS, Zollinger L V., Morton KA, Butterfield RI, Kadrmas DJ, Christian PE, et al. Comparison of 18F-fluorodeoxyglucose and 18F-fluorothymidine PET in differentiating radiation necrosis from recurrent glioma. Clin Nucl Med. 2012;37:854–861. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22889774.

Li Z, Yu Y, Zhang H, Xu G, Chen L. A meta-analysis comparing 18F-FLT PET with 18F-FDG PET for assessment of brain tumor recurrence. Nucl Med Commun. 2015;36:695–701. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25768337.

10.

Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med. 2008;49:694–9. Available from: http://jnm.snmjournals.org/cgi/doi/10.2967/jnumed.107.048082.CrossRefPubMed

11.

Minamimoto R, Saginoya T, Kondo C, Tomura N, Ito K, Matsuo Y, et al. Differentiation of brain tumor recurrence from post-radiotherapy necrosis with ¹¹C-methionine PET: visual assessment versus quantitative assessment. PLoS One. 2015;10:1–13.CrossRef

12.

Takenaka S, Asano Y, Shinoda J, Nomura Y, Yonezawa S, Miwa K, et al. Comparison of (11)C-methionine, (11)C-choline, and (18)F-fluorodeoxyglucose-PET for distinguishing glioma recurrence from radiation necrosis. Neurol Med Chir (Tokyo). 2014;54:280–9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24305028.

13.

Asao C, Korogi Y, Kitajima M, Hirai T, Baba Y, Makino K, et al. Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence. Am J Neuroradiol. 2005;26:1455–60.PubMed

14.

Hatzoglou V, Ulaner GA, Zhang Z, Beal K, Holodny AI, Young RJ. Comparison of the effectiveness of MRI perfusion and fluorine-18 FDG PET-CT for differentiating radiation injury from viable brain tumor: a preliminary retrospective analysis with pathologic correlation in all patients. Clin Imaging. 2013;37:451–457. Elsevier Inc. Available from: https://doi.org/10.1016/j.clinimag.2012.08.008.

15.

Sundgren PC. MR spectroscopy in radiation injury. Am J Neuroradiol. 2009;30:1469–76. Available from: http://www.ajnr.org/cgi/doi/10.3174/ajnr.A1580.CrossRefPubMed

16.

Shah R, Vattoth S, Jacob R, Manzil FF, O’Malley JP, Borghei P, et al. Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence. Radiographics. 2012;32:1343–59. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22977022.CrossRefPubMed

17.

Rojo F, García-Parra J, Zazo S, Tusquets I, Ferrer-Lozano J, Menendez S, et al. Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer. Ann Oncol. 2012;23:1156–64.CrossRefPubMed

18.

Byers LA, Wang J, Nilsson MB, Fujimoto J, Saintigny P, Yordy J, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2012;2:798–811.CrossRefPubMedPubMedCentral

19.

Zaremba T, Ketzer P, Cole M, Coulthard S, Plummer ER, Curtin NJ. Poly(ADP-ribose) polymerase-1 polymorphisms, expression and activity in selected human tumour cell lines. Br J Cancer. 2009;101:256–262. Nature Publishing Group. Available from: https://doi.org/10.1038/sj.bjc.6605166.

20.

Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.CrossRefPubMed

21.

Swindall AF, Stanley JA, Yang ES. PARP-1: friend or foe of DNA damage and repair in tumorigenesis? Cancers (Basel). 2013;5:943–58.CrossRef

22.

Nosho K, Yamamoto H, Mikami M, Taniguchi H, Takahashi T, Adachi Y, et al. Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis. Eur J Cancer. 2006;42:2374–2381. Elsevier Ltd. Available from: https://doi.org/10.1016/j.ejca.2006.01.061.

23.

Schiewer MJ, Knudsen KE. Transcriptional roles of PARP1 in cancer. Mol Cancer Res. 2014;12:1069–80. Available from: http://mcr.aacrjournals.org/cgi/doi/10.1158/1541-7786.MCR-13-0672.CrossRefPubMedPubMedCentral

24.

Yelamos J, Farres J, Llacuna L, Ampurdanes C, Martin-Caballero J. PARP-1 and PARP-2: new players in tumour development. Am J Cancer Res. 2011;1:328–46. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180065/.

25.

Tang J, Salloum D, Carney B, Brand C, Kossatz S, Sadique A, et al. Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma. Proc Natl Acad Sci. 2017;114:E7441–9. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1705013114.CrossRefPubMed

26.

Carney B, Carlucci G, Salinas B, Di Gialleonardo V, Kossatz S, Vansteene A, et al. Non-invasive PET imaging of PARP1 expression in glioblastoma models. Mol Imaging Biol. 2016;18:386–92.CrossRefPubMedPubMedCentral

27.

Knight JC, Koustoulidou S, Cornelissen B. Imaging the DNA damage response with PET and SPECT. Eur J Nucl Med Mol Imaging. 2017;44:1065–78.CrossRefPubMedPubMedCentral

28.

Galldiks N, Langen KJ. Amino acid PET—an imaging option to identify treatment response, posttherapeutic effects, and tumor recurrence? Front Neurol. 2016;7:1–7.CrossRef

29.

Galldiks N, Langen K-J, Pope WB. From the clinician’s point of view—what is the status quo of positron emission tomography in patients with brain tumors? Neuro Oncol. 2015;17:1434–44. Available from: https://academic.oup.com/neuro-oncology/article-lookup/doi/10.1093/neuonc/nov118.CrossRefPubMedPubMedCentral

30.

Spaeth N, Wyss MT, Weber B, Scheidegger S, Lutz A, Verwey J, et al. Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence. J Nucl Med. 2004;45:1931–8. Available from: http://jnm.snmjournals.org/content/45/11/1931.long.

31.

Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, et al. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514:291–302. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0005273601003844.CrossRefPubMed

32.

Wagner CA, Lang F, Bröer S. Function and structure of heterodimeric amino acid transporters. Am J Physiol Cell Physiol. 2001;281:C1077–93. Available from: http://www.physiology.org/doi/10.1152/ajpcell.2001.281.4.C1077.CrossRefPubMed

33.

Habermeier A, Graf J, Sandhöfer BF, Boissel JP, Roesch F, Closs EI. System l amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-l-tyrosine (FET). Amino Acids. 2015;47:335–44.CrossRefPubMed

34.

Lahoutte T, Caveliers V, Camargo SMR, Franca R, Ramadan T, Veljkovic E, et al. SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation. J Nucl Med. 2004;45:1591–6.PubMed

35.

Menear KA, Adcock C, Boulter R, Cockcroft X, Copsey L, Cranston A, et al. Novel bioavailable inhibitor of poly (ADP-ribose ) polymerase-1. J Med Chem. 2018;51(20):6581–91.

36.

Hamacher K, Coenen HH. Efficient routine production of the 18F-labelled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine. Appl Radiat Isot. 2002;57:853–6.CrossRefPubMed

37.

Jiang X, Yuan L, Engelbach JA, Cates J, Perez-Torres CJ, Gao F, et al. A gamma-knife-enabled mouse model of cerebral single-hemisphere delayed radiation necrosis. PLoS One. 2015;10:1–13.

38.

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82.CrossRefPubMed

39.

Ikotun OF, Marquez BV, Huang C, Masuko K, Daiji M, Masuko T, et al. Imaging the L-type amino acid transporter-1 (LAT1) with Zr-89 ImmunoPET. PLoS One. 2013;8:1–9.CrossRef

40.

Galldiks N, Stoffels G, Filss CP, Piroth MD, Sabel M, Ruge MI, et al. Role of O-(2-18F-fluoroethyl)-L-tyrosine PET for differentiation of local recurrent brain metastasis from radiation necrosis. J Nucl Med. 2012;53:1367–74. Available from: http://jnm.snmjournals.org/cgi/doi/10.2967/jnumed.112.103325.CrossRefPubMed

41.

Kossatz S, Carney B, Schweitzer M, Carlucci G, Miloushev VZ, Maachani UB, et al. Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models. Cancer Res. 2017;77:2112–23.CrossRefPubMedPubMedCentral

42.

Murnyák B, Kouhsari MC, Hershkovitch R, Kálmán B, Marko-Varga G, Klekner Á, et al. PARP1 expression and its correlation with survival is tumour molecular subtype dependent in glioblastoma. Oncotarget. 2017;8:46348–62. Available from: http://www.oncotarget.com/fulltext/18013.CrossRefPubMedPubMedCentral

43.

Papin-Michault C, Bonnetaud C, Dufour M, Almairac F, Coutts M, Patouraux S, et al. Study of LAT1 expression in brain metastases: towards a better understanding of the results of positron emission tomography using amino acid tracers. PLoS One. 2016;11(6):e0157139.

44.

Lumniczky K, Szatmári T, Sáfrány G. Ionizing radiation-induced immune and inflammatory reactions in the brain. Front Immunol. 2017;8:1–13.CrossRef

45.

Vatner RE, Formenti SC. Myeloid-derived cells in tumors: effects of radiation. Semin Radiat Oncol. 2015;25:18–27. Elsevier. Available from: https://doi.org/10.1016/j.semradonc.2014.07.008.

46.

Moravan MJ, Olschowka JA, Williams JP, O’Banion MK. Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling. J Neuroinflammation. 2016;13:30. Available from: https://doi.org/10.1186/s12974-016-0496-8.CrossRefPubMedPubMedCentral

47.

Stöber B, Tanase U, Herz M, Seidl C, Schwaiger M, Senekowitsch-Schmidtke R. Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L- tyrosine (FET) uptake in human tumour and inflammatory cells. Eur J Nucl Med Mol Imaging. 2006;33:932–9.CrossRefPubMed

48.

Werner A, Koschke M, Leuchtner N, Luckner-Minden C, Habermeier A, Rupp J, et al. Reconstitution of T cell proliferation under arginine limitation: activated human T cells take up citrulline via L-type amino acid transporter 1 and use it to regenerate arginine after induction of argininosuccinate synthase expression. Front Immunol. 2017;8:864.

49.

Yoon BR, Oh Y-J, Kang SW, Lee EB, Lee W-W. Role of SLC7A5 in metabolic reprogramming of human monocyte/macrophage immune responses. Front Immunol. 2017;9:53. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2018.00053/full.

50.

Rau FC, Weber WA, Wester HJ, Herz M, Becker I, Krüger A, et al. O-(2-[18F]fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes. Eur J Nucl Med. 2002;29:1039–46.CrossRef

51.

Wyss MT, Weber B, Honer M, Späth N, Ametamey SM, Westera G, et al. 18F-choline in experimental soft tissue infection assessed with autoradiography and high-resolution PET. Eur J Nucl Med Mol Imaging. 2004;31:312–6.CrossRefPubMed

52.

Kaim AH, Weber B, Kurrer MO, Westera G, Schweitzer A, Gottschalk J, et al. (18)F-FDG and (18)F-FET uptake in experimental soft tissue infection. Eur J Nucl Med Mol Imaging. 2002;29:648–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11976803%5Cnhttp://link.springer.com/10.1007/s00259-002-0780-y.CrossRefPubMed

53.

Schinkel AH. P-glycoprotein, a gatekeeper in the blood–brain barrier. Adv Drug Deliv Rev. 1999;36:179–94. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0169409X98000854.CrossRefPubMed

54.

Vaidyanathan A, Sawers L, Gannon AL, Chakravarty P, Scott AL, Bray SE, et al. ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. Br J Cancer. 2016;115:431–441. Nature Publishing Group. Available from: https://doi.org/10.1038/bjc.2016.203.

Title: Discriminating radiation injury from recurrent tumor with [18F]PARPi and amino acid PET in mouse models
Authors: Patrick L. Donabedian
Susanne Kossatz
John A. Engelbach
Stephen A. Jannetti
Brandon Carney
Robert J. Young
Wolfgang A. Weber
Joel R. Garbow
Thomas Reiner
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2018
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-018-0399-z

At a glance: The STEP trials

Springer Medicine

Discriminating radiation injury from recurrent tumor with [¹⁸F]PARPi and amino acid PET in mouse models

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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