Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients

Purpose: The purpose of the study is to assess the contribution of 18F-fluoro-ethyl-tyrosine (18F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. Materials and methods: The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate 18F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTVMRI). PET image segmentation techniques included manual delineation of contours (GTVman), a 2.5 standardized uptake value (SUV) cutoff (GTV2.5), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV40% and GTV50%), signal-to-background ratio (SBR)-based adaptive thresholding (GTVSBR), gradient find (GTVGF), and region growing (GTVRG). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Results: Contours defined using GTV2.5 failed to provide successful delineation technically in three patients (18% of cases) as SUVmax < 2.5 and clinically in 14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based techniques were usually smaller than GTVMRI (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTVMRI in six patients (33% of cases). Conclusions: The selection of the most appropriate 18F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineatio

Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE. NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p &gt; 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine

Initial experience with an 11 MeV self-shielded medical cyclotron on operation and radiation safety

A self-shielded medical cyclotron (11 MeV) was commissioned at our center, to produce positron emitters, namely, 18F, 15O, 13N and 11C for positron emission tomography (PET) imaging. Presently the cyclotron has been exclusively used for the production of 18F- for 18F-FDG imaging. The operational parameters which influence the yield of 18F- production were monitored. The radiation levels in the cyclotron and radiochemistry laboratory were also monitored to assess the radiation safety status in the facility. The target material, 18O water, is bombarded with proton beam from the cyclotron to produce 18F- ion that is used for the synthesis of 18F-FDG. The operational parameters which influence the yield of 18F- were observed during 292 production runs out of a total of more than 400 runs. The radiation dose levels were also measured in the facility at various locations during cyclotron production runs and in the radiochemistry laboratory during 18F-FDG syntheses. It was observed that rinsing the target after delivery increased the number of production runs in a given target, as well as resulted in a better correlation between the duration of bombardment and the end of bombardment 18F- activity with absolutely clean target after being rebuilt. The radiation levels in the cyclotron and radiochemistry laboratory were observed to be well within prescribed limits with safe work practice

225Ac and 213Bi alpha-Particle-Emitter Therapy in Combination with SAHA and 17-AAG

Alpha-particle emitter radiopharmaceutical therapy (alpha-RPT) is a promising approach to cancer therapy. Alpha-particles lead to highly disruptive and largely irreparable deoxy ribonucleic acid (DNA) double strand breaks capable of killing a cell with as few as one to two tracks through the nucleus. Although the ability to repair alpha-induced DNA damage is independent of alpha-dose-rate the efficacy of alphaemitter with a long half-life can be compromised when targeting very rapidly proliferating tumor cells if the dose-rate is outpaced by the proliferation rate. In this study, we investigate alpha-particle emitter radiopharmaceutical therapy (alpha-RPT) using 225Ac (T1/2=10 days) and 213Bi (T1/2=45.6 min) in combination with clinically approved tumor growth suppressor, suberoylanilide hydroxamic acid (SAHA) and cell cycle blocker, 17-(Allylamino)-17-demethoxy- geldanamycin (17-AAG) in breast cancer cells.JRC.E.5-Nuclear chemistr

Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients

PURPOSE: The purpose of the study is to assess the contribution of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. MATERIALS AND METHODS: The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate (18)F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image segmentation techniques included manual delineation of contours (GTV(man)), a 2.5 standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and region growing (GTV(RG)). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. RESULTS: Contours defined using GTV(2.5) failed to provide successful delineation technically in three patients (18% of cases) as SUV(max) < 2.5 and clinically in 14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based techniques were usually smaller than GTV(MRI) (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTV(MRI) in six patients (33% of cases). CONCLUSIONS: The selection of the most appropriate (18)F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation