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

Jeroen Verhoeven (UGent) , Julie Bolcaen (UGent) , Valerie De Meulenaere (UGent) , Ken Kersemans (UGent) , Benedicte Descamps (UGent) , Sam Donche (UGent) , Caroline Van den Broecke (UGent) , Tom Boterberg (UGent) , Jean-Pierre Kalala Okito (UGent) , Karel Deblaere (UGent) , et al.
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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 x 5 mm(2)) 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 x 1 mm(2)) delivered to the region either with maximum [F-18]FET or [F-18]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 D-90-, D-50- and D-2- 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 D-2-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.
Keywords
Glioblastoma, PET boosting, FET, FAZA, Radiotherapy, Preclinical, INTEGRATED X-RAY, RADIATION-THERAPY, MULTIFORME, TEMOZOLOMIDE, GLIOMA, TUMORS, CLASSIFICATION, IRRADIATION, CONCOMITANT, SYSTEM

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MLA
Verhoeven, Jeroen et al. “Technical Feasibility of [18F]FET and [18F]FAZA PET Guided Radiotherapy in a F98 Glioblastoma Rat Model.” RADIATION ONCOLOGY 14 (2019): n. pag. Print.
APA
Verhoeven, J., Bolcaen, J., De Meulenaere, V., Kersemans, K., Descamps, B., Donche, S., Van den Broecke, C., et al. (2019). Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model. RADIATION ONCOLOGY, 14.
Chicago author-date
Verhoeven, Jeroen, Julie Bolcaen, Valerie De Meulenaere, Ken Kersemans, Benedicte Descamps, Sam Donche, Caroline Van den Broecke, et al. 2019. “Technical Feasibility of [18F]FET and [18F]FAZA PET Guided Radiotherapy in a F98 Glioblastoma Rat Model.” Radiation Oncology 14.
Chicago author-date (all authors)
Verhoeven, Jeroen, Julie Bolcaen, Valerie De Meulenaere, Ken Kersemans, Benedicte Descamps, Sam Donche, Caroline Van den Broecke, Tom Boterberg, Jean-Pierre Kalala Okito, Karel Deblaere, Christian Vanhove, Filip De Vos, and Ingeborg Goethals. 2019. “Technical Feasibility of [18F]FET and [18F]FAZA PET Guided Radiotherapy in a F98 Glioblastoma Rat Model.” Radiation Oncology 14.
Vancouver
1.
Verhoeven J, Bolcaen J, De Meulenaere V, Kersemans K, Descamps B, Donche S, et al. Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model. RADIATION ONCOLOGY. 2019;14.
IEEE
[1]
J. Verhoeven et al., “Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model,” RADIATION ONCOLOGY, vol. 14, 2019.
@article{8617614,
  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 x 5 mm(2)) 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 x 1 mm(2)) delivered to the region either with maximum [F-18]FET or [F-18]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 D-90-, D-50- and D-2- 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 D-2-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.},
  articleno    = {11},
  author       = {Verhoeven, Jeroen and Bolcaen, Julie and De Meulenaere, Valerie and Kersemans, Ken and Descamps, Benedicte and Donche, Sam and Van den Broecke, Caroline and Boterberg, Tom and Kalala Okito, Jean-Pierre and Deblaere, Karel and Vanhove, Christian and De Vos, Filip and Goethals, Ingeborg},
  issn         = {1748-717X},
  journal      = {RADIATION ONCOLOGY},
  keywords     = {Glioblastoma,PET boosting,FET,FAZA,Radiotherapy,Preclinical,INTEGRATED X-RAY,RADIATION-THERAPY,MULTIFORME,TEMOZOLOMIDE,GLIOMA,TUMORS,CLASSIFICATION,IRRADIATION,CONCOMITANT,SYSTEM},
  language     = {eng},
  title        = {Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model},
  url          = {http://dx.doi.org/10.1186/s13014-019-1290-4},
  volume       = {14},
  year         = {2019},
}

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