Dataset Information

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

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.

SUBMITTER: Verhoeven J

PROVIDER: S-EPMC6543630 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Technical feasibility of [<sup>18</sup>F]FET and [<sup>18</sup>F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model.

Verhoeven Jeroen J Bolcaen Julie J De Meulenaere Valerie V Kersemans Ken K Descamps Benedicte B Donche Sam S Van den Broecke Caroline C Boterberg Tom T Kalala Jean-Pierre JP Deblaere Karel K Vanhove Christian C De Vos Filip F Goethals Ingeborg I

Radiation oncology (London, England) 20190530 1

<h4>Background</h4>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.<h4>Method</h4>F98 GB cells inoculated in the rat brain w ...[more]

PMID: 31146757

Similar Datasets

Project description:PurposeGlioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [18F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [18F]FET and [18F]fluciclovine using PET pharmacokinetic modeling (PKM).Methods[18F]rhPSMA-7.3, [18F]FET, and [18F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq (n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation.Results[18F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1-2.5, in 15-60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution VT (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [18F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and VS (1.3/0.7, p < 0.05, tumor) compared to [18F]FET and LA indicated reversible binding. VT increased (p < 0.001, tumor, 21 to 28 days) for [18F]FET (0.5-1.4) and [18F]fluciclovine (0.84-1.5).Conclusion[18F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [18F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [18F]fluciclovine was superior to [18F]FET rendering it more suitable for PET imaging of GBM.

Project description:BackgroundGlioma grading with dynamic 18F-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour. This work aimed to ensure a reader-independent glioma characterisation and identification of aggressive sub-volumes by performing a voxel-based analysis with diagnostically relevant kinetic and static 18F-FET PET parameters. One hundred sixty-two patients with a newly diagnosed glioma classified according to histologic and molecular genetic properties were evaluated. The biological tumour volume (BTV) was segmented in static 20-40 min p.i. 18F-FET PET images using the established threshold of 1.6?×?background activity. For each enclosed voxel, the time-to-peak (TTP), the late slope (Slope15-40), and the tumour-to-background ratios (TBR5-15, TBR20-40) obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The percentage portion of these values within the BTV was evaluated with percentage volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The ability to differentiate histologic and molecular genetic classes was assessed and compared to volume-of-interest (VOI)-based parameters.ResultsAggressive WHO grades III and IV and IDH-wildtype gliomas were dominated by a high proportion of voxels with an early peak, negative slope, and high TBR, whereby the PVHs with TTP <?20 min p.i., Slope15-40 <?0 SUV/h, and TBR5-15 and TBR20-40 >?2 yielded the most significant differences between glioma grades. We found significant differences of the parameters between WHO grades and IDH mutation status, where the effect size was predominantly higher for voxel-based PVHs compared to the corresponding VOI-based parameters. A low overlap of BTV sub-volumes defined by TTP <?20 min p.i. and negative Slope15-40 with TBR5-15?>?2- and TBR20-40?>?2-defined hotspots was observed.ConclusionsThe presented approach applying voxel-wise analysis of dynamic 18F-FET PET enables an enhanced characterisation of gliomas and might potentially provide a fast identification of aggressive sub-volumes within the BTV. Parametric 3D 18F-FET PET information as investigated in this study has the potential to guide individual therapy instrumentation and may be included in future biopsy studies.

Project description:BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100?°C. Subsequently, a droplet containing 60?nmol of precursor was added to the chip and the fluorination reaction was performed at 90?°C for 5?min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90?°C for 3?min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55?±?7% (n?=?4) after purification and formulation. When automated, the synthesis could be completed in 35?min. Starting with <?370?MBq of activity, ~?150?MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119?GBq/?mol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48?GBq/?mol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.

Dataset Information

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

Background

Method

Results

Conclusion

Publications

Technical feasibility of [<sup>18</sup>F]FET and [<sup>18</sup>F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Method

Results

Conclusion

Publications

Technical feasibility of [<sup>18</sup>F]FET and [<sup>18</sup>F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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