Dosimetric impact of amino acid positron emission tomography imaging for target delineation in radiation treatment planning for high-grade gliomas

Background and purpose: The amino-acid positron emission tomography (PET) tracer 3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine (18F-DOPA) has increased sensitivity for detecting regions of biologically aggressive tumors compared to T1 contrast-enhanced (T1-CE) magnetic resonance imaging (MRI). We performed dosimetric evaluation of treatment plans prepared with and without inclusion of 18F-DOPA-based biological target volume (BTV) evaluating its role in guiding radiotherapy of grade III/IV gliomas. Materials and methods: Eight patients (five T1-CE, three non-contrast-enhancing [NCE]) were included in our study. MRI only-guided anatomic plans and MRI+18FDOPA-PET-guided biologic plans were prepared for each patient, and dosimetric data for target volumes and organs at risk (OAR) were compared. High-dose BTV60Gy was defined as regions with tumor to normal brain (T/N) >2.0, while low-dose BTV51Gy was initially based on T/N >1.3, but refined per Nuclear Medicine expert. Results: For T1-CE tumors, planning target volumes (PTV) were larger than MRI-only anatomic target volumes. Despite increases in size of both gross target volumes and PTV, with volumetric-modulated arc therapy planning, no increase of dose to OAR was observed while maintaining similar target dose coverage. For NCE tumors, MRI+18F-DOPA PET biologic imaging identified a sub-region of the large, T2-FLAIR abnormal signal which may allow a smaller volume to receive the high dose (60 Gy) radiation. Conclusions: For T1-CE tumors, PTVs were larger than MRI-only anatomic target volumes with no increase of dose to OARs. Therefore, MRI+18F-DOPA PET-based biologic treatment planning appears feasible in patients with high-grade gliomas. Keywords: 18F-DOPA PET, PET-guided radiation therapy, Planning study, Amino acid PE

Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M−P− in 16%, M−P+ in 32%, M+P+ in 46% and M+P− in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning

Anemia contributes to cardiovascular disease through reductions in nitric oxide

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Last word on viewpoint: Anemia contributes to cardiovascular disease through reductions in nitric oxide

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An image-based skeletal dosimetry model for the ICRP reference adult male—internal electron sources

Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, are imposed through detailed analyses of whole-body ex-vivo CT images (1 mm resolution) and spongiosa-specific ex-vivo microCT images (30 μm resolution), respectively, taken from a 40-year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP’s change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10-μm endosteal layer covering the trabecular and cortical surfaces, to a 50-μm shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal-averaged values of absorbed fraction in the present model are noted to be very compatible with those weighted by the skeletal tissue distributions found in the ICRP Publication 110 adult male and female voxel phantoms, but are in many cases incompatible with values used in current and widely implemented internal dosimetry software