Top

Published in:

Open Access 01-12-2019 | Glioblastoma | Research

Technical feasibility of [¹⁸F]FET and [¹⁸F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model

Authors: Jeroen Verhoeven, Julie Bolcaen, Valerie De Meulenaere, Ken Kersemans, Benedicte Descamps, Sam Donche, Caroline Van den Broecke, Tom Boterberg, Jean-Pierre Kalala, Karel Deblaere, Christian Vanhove, Filip De Vos, Ingeborg Goethals

Published in: Radiation Oncology | Issue 1/2019

Abstract

Background

Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part.

Method

F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm²) was delivered to the target volume delineated based on T1w MRI for three treatment groups. Two of those treatment groups received an additional radiation boost of 5 Gy (1 × 1 mm²) delivered to the region either with maximum [¹⁸F]FET or [¹⁸F]FAZA PET tracer uptake, respectively. All therapy groups received intraperitoneal (IP) injections of TMZ. Finally, a control group received no RT and only control IP injections. The average, minimum and maximum dose, as well as the D₉₀-, D₅₀- and D₂- values were calculated for nine rats using both RT plans. To evaluate response to therapy, follow-up tumor volumes were delineated based on T1w MRI.

Results

When comparing the dose volume histograms, a significant difference was found exclusively between the D₂-values. A significant difference in tumor growth was only found between active therapy and sham therapy respectively, while no significant differences were found when comparing the three treatment groups.

Conclusion

In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.

Available only for authorised users

Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492–507. https://doi.org/10.1056/NEJMra0708126.CrossRefPubMed

Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. https://doi.org/10.1007/s00401-007-0243-4.CrossRefPubMedPubMedCentral

Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–20. https://doi.org/10.1007/s00401-016-1545-1.CrossRefPubMed

Anton K, Baehring JM, Mayer T. Glioblastoma Multiforme: Overview of Current Treatment and Future Perspectives. Hematol Oncol Clin North Am. 2012;26:825–53. https://doi.org/10.1016/j.hoc.2012.04.006.CrossRefPubMed

Allen NJ, Barres BA. Neuroscience: glia - more than just brain glue. Nature. 2009;457:675–7. https://doi.org/10.1038/457675a.CrossRefPubMed

Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant Temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. https://doi.org/10.1056/NEJMoa043330.CrossRefPubMed

Stupp BR, Dietrich P, Kraljevic SO, et al. Glioblastoma Multiforme treated with concomitant radiation plus Temozolomide followed by adjuvant temozolomide. J Clin Oncol. 2002;20:1375–82.CrossRefPubMed

Austin-Seymour M, Chen GTY, Rosenman J, et al. Tumor and target delineation: current research and future challenges. Int J Radiat Oncol Biol Phys. 1995;33:1041–52. https://doi.org/10.1016/0360-3016(95)00215-4.CrossRefPubMed

Burnet NG, Thomas SJ, Burton KE, et al (2004) Defining the tumour and target volumes for radiotherapy. Cancer Imaging. 2004;4(2):153–61. https://doi.org/10.1102/1470-7330.2004.0054.CrossRefPubMedPubMedCentral

10.

Berthelsen AK, Dobbs J, Kjellen E, et al. What’s new in target volume definition for radiologists in ICRU report 71 ? How can the ICRU volume definitions be integrated in clinical practice ? Cancer Imaging. 2007;7:104–16 https://doi.org/10.1102/1470-7330.2007.0013.CrossRefPubMedPubMedCentral

11.

Ling CC, Humm J, Larson S, et al. Towards multidimensional radiotherapy ((MD)CRT): biological imaging and biological conformality. Int J Radition Oncol Biol Phys. 2000;47:551–60.CrossRef

12.

Trani D, Reniers B, Persoon L, et al. What level of accuracy is achievable for preclinical dose painting studies on a clinical irradiation platform? Radiat Res. 2015;183:501–10 https://doi.org/10.1667/RR13933.1.CrossRefPubMed

13.

Grosu AL, Weber WA, Franz M, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radition Oncol Biol Phys. 2005;63:511–9 https://doi.org/10.1016/j.ijrobp.2005.01.056.CrossRef

14.

Trani D, Yaromina A, Dubois L, et al. Preclinical assessment of efficacy of radiation dose painting based on Intratumoral FDG-PET uptake. Clin Cancer Res. 2015;21:5511–8 https://doi.org/10.1158/1078-0432.CCR-15-0290.CrossRefPubMed

15.

Nowosielski M, DiFranco MD, Putzer D, et al. An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-grade gliomas. PLoS One. 2014;9:e95830 https://doi.org/10.1371/journal.pone.0095830.CrossRefPubMedPubMedCentral

16.

Haubner R. PET radiopharmaceuticals in radiation treatment planning - synthesis and biological characteristics. Radiother Oncol. 2010;96:280–7 https://doi.org/10.1016/j.radonc.2010.07.022.CrossRefPubMed

17.

Di Perri D, Lee JA, Bol A, et al. Correlation analysis of [18F]fluorodeoxyglucose and [18F]fluoroazomycin arabinoside uptake distributions in lung tumours during radiation therapy. Acta Oncol (Madr). 2017;56:1181–8 https://doi.org/10.1080/0284186X.2017.1329594.CrossRef

18.

Thorwarth D. Functional imaging for radiotherapy treatment planning: current status and future directions - a review. Br J Radiol. 2015;88 https://doi.org/10.1259/bjr.20150056.CrossRefPubMedPubMedCentral

19.

Barth RF, Kaur B. Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas. J Neuro-Oncol. 2009;94:299–312 https://doi.org/10.1007/s11060-009-9875-7.CrossRef

20.

Bryant MJ, Chuah TL, Luff J, et al. A novel rat model for glioblastoma multiforme using a bioluminescent F98 cell line. J Clin Neurosci. 2008;15:545–51 https://doi.org/10.1016/j.jocn.2007.04.022.CrossRefPubMed

21.

Jacobs VL, Valdes PA, Hickey WF, De Leo JA. Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model. ASN Neuro. 2011;3:AN20110014 https://doi.org/10.1042/an20110014.CrossRef

22.

de Vries NA, Beijnen JH, van Tellingen O. High-grade glioma mouse models and their applicability for preclinical testing. Cancer Treat Rev. 2009;35:714–23 https://doi.org/10.1016/j.ctrv.2009.08.011.CrossRefPubMed

23.

Bolcaen J, Descamps B, Boterberg T, et al. PET and MRI guided irradiation of a glioblastoma rat model using a micro-irradiator. J Vis Exp. 2017:1–10 https://doi.org/10.3791/56601.

24.

Verhoeven J, Hulpia F, Kersemans K, et al. New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma. Sci Rep. 2019;9:2878 https://doi.org/10.1038/s41598-019-40013-x.

25.

Bolcaen J, Lybaert K, Moerman L, et al. Kinetic modeling and graphical analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between high-grade glioma and radiation necrosis in rats. PLoS One. 2016;11:e0161845 https://doi.org/10.1371/journal.pone.0161845.CrossRefPubMedPubMedCentral

26.

Bolcaen J, Descamps B, Deblaere K, et al. (18)F-fluoromethylcholine (FCho), (18)F-fluoroethyltyrosine (FET), and (18)F-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma and radiation necrosis in rats: a PET study. Nucl Med Biol. 2014; https://doi.org/10.1016/j.nucmedbio.2014.07.006.CrossRefPubMed

27.

Robinson CG, Palomo JM, Rahmathulla G, et al. Effect of alternative temozolomide schedules on glioblastoma O 6-methylguanine-DNA methyltransferase activity and survival. Br J Cancer. 2010;103:498–504 https://doi.org/10.1038/sj.bjc.6605792.CrossRefPubMedPubMedCentral

28.

Banissi C, Ghiringhelli F, Chen L, Carpentier AF. Treg depletion with a low-dose metronomic temozolomide regimen in a rat glioma model. Cancer Immunol Immunother. 2009;58:1627–34 https://doi.org/10.1007/s00262-009-0671-1.CrossRefPubMed

29.

Bolcaen J, Descamps B, Deblaere K, et al. MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the small animal radiation research platform (SARRP). J Neuro-Oncol. 2014;120:257–66 https://doi.org/10.1007/s11060-014-1552-9.CrossRefPubMed

30.

Diaz RJ, Ali S, Qadir MG, et al. The role of bevacizumab in the treatment of glioblastoma. J Neuro-Oncol. 2017;133:455–67 https://doi.org/10.1007/s11060-017-2477-x.CrossRefPubMed

31.

Seystahl K, Gramatzki D, Roth P, Weller M. Pharmacotherapies for the treatment of glioblastoma – current evidence and perspectives. Expert Opin Pharmacother. 2016;17:1259–70 https://doi.org/10.1080/14656566.

32.

Badiyan SN, Markovina S, Simpson JR, et al. Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide. Int J Radiat Oncol Biol Phys. 2014;90:877–85 https://doi.org/10.1016/j.ijrobp.2014.07.014.CrossRefPubMed

33.

Menichetti L, Petroni D, Panetta D, et al. A micro-PET/CT approach using O-(2-[18F]fluoroethyl)-l-tyrosine in an experimental animal model of F98 glioma for BNCT. Appl Radiat Isot. 2011;69:1717–20 https://doi.org/10.1016/j.apradiso.2011.02.037.CrossRefPubMed

34.

Shi J, Udayakumar TS, Wang Z, et al. Optical molecular imaging-guided radiation therapy part 1: integrated x-ray and bioluminescence tomography. Med Phys. 2017;44:4786–94 https://doi.org/10.1002/mp.12415.CrossRefPubMed

35.

Shi J, Udayakumar TS, Wang Z, et al. Optical molecular imaging-guided radiation therapy part 2: integrated x-ray and fluorescence molecular tomography. Med Phys. 2017;44:4795–803 https://doi.org/10.1002/mp.12414.CrossRefPubMed

36.

Yang Y, Wang KKH, Eslami S, et al. Systematic calibration of an integrated x-ray and optical tomography system for preclinical radiation research. Med Phys. 2015;42:1710–20 https://doi.org/10.1118/1.4914860.CrossRefPubMedPubMedCentral

37.

Zhang B, Kang-Hsin Wang K, Yu J, et al. Bioluminescence tomography guided radiation therapy for preclinical research. Bin Int J Radiat Oncol Biol Phys. 2016;94:1144–53 https://doi.org/10.1016/j.ijrobp.2015.11.039.CrossRef

38.

Weersink RA, Ansell S, Wang A, et al. Integration of optical imaging with a small animal irradiator. Med Phys. 2014;41 https://doi.org/10.1118/14894730.

39.

Luker GD, Luker KE. Optical Imaging : current applications and future directions. J Nucl Med. 2008;49:1–4 https://doi.org/10.2967/jnumed.107.045799.CrossRefPubMed

40.

Donche S, Verhoeven J, Descamps B, et al. The path toward PET-guided radiation therapy for glioblastoma in laboratory animals: a mini review. Front Med. 2019;6:1–9 https://doi.org/10.3389/fmed.2019.00005.CrossRef

41.

Belloli S, Brioschi A, Politi LS, et al. Characterization of biological features of a rat F98 GBM model: a PET-MRI study with [18F]FAZA and [18F]FDG. Nucl Med Biol. 2013;40:831–40 https://doi.org/10.1016/j.nucmedbio.2013.05.004.CrossRefPubMed

42.

Bolcaen J, Descamps B, Deblaere K, et al. F18-fluoromethylcholine (FCho), F18-fluoroethyltyrosine (FET) and F18-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma (HGG) and radiation necrosis (RN): a {mu}PET study. Soc Nucl Med Annu Meet Abstr. 2015;42:38–45 https://doi.org/10.1016/j.nucmedbio.2014.07.006.

43.

Taylor A, Powell MEB. Intensity-modulated radiotherapy - what is it? Cancer Imaging. 2004;4:68–73 https://doi.org/10.1102/1470-7330.2004.0003.CrossRefPubMedPubMedCentral

44.

Schültke E, Bräuer-Krisch E, Blattmann H, et al. Survival of rats bearing advanced intracerebral F 98 tumors after glutathione depletion and microbeam radiation therapy: conclusions from a pilot project. Radiat Oncol. 2018;13:1–11 https://doi.org/10.1186/s13014-018-1038-6.CrossRef

45.

Lenting K, Verhaak R, ter Laan M, et al. Glioma: experimental models and reality. Acta Neuropathol. 2017;133:263–82 https://doi.org/10.1007/s00401-017-1671-4.CrossRefPubMedPubMedCentral

Title: Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model
Authors: Jeroen Verhoeven
Julie Bolcaen
Valerie De Meulenaere
Ken Kersemans
Benedicte Descamps
Sam Donche
Caroline Van den Broecke
Tom Boterberg
Jean-Pierre Kalala
Karel Deblaere
Christian Vanhove
Filip De Vos
Ingeborg Goethals
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Glioblastoma
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Glioblastoma
Radiotherapy
Positron Emission Tomography
Glioblastoma
Published in: Radiation Oncology / Issue 1/2019
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-019-1290-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Technical feasibility of [¹⁸F]FET and [¹⁸F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model

Abstract

Background

Method

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2019

Circular collimator arc versus dynamic conformal arc treatment planning for linac-based stereotactic radiosurgery of an intracranial small single lesion: a perspective of lesion asymmetry

Impact of sex on the prognosis of patients with esophageal squamous cell cancer underwent definitive radiotherapy: a propensity score-matched analysis

Infiltration tendency of internal mammary lymph nodes involvement in patients with breast cancer: anatomical characteristics and implications for target delineation

Impact of adaptive intensity-modulated radiotherapy on the neutrophil-to-lymphocyte ratio in patients with nasopharyngeal carcinoma

Changes of lung parenchyma density following high dose radiation therapy for thoracic carcinomas – an automated analysis of follow up CT scans

Adaptive step size algorithm to increase efficiency of proton macro Monte Carlo dose calculation