Neuro-oncology imaging roadmap: FDG PET → amino acid PET → SSTR2 theranostics in meningioma
Ordinary sugar-based PET scans do not work well in the brain because healthy brain tissue itself uses a lot of sugar. Nuclear medicine had to develop tracers that light up brain tumours specifically, first amino acid tracers for gliomas and then a receptor tracer that also opens the door to a matched radioactive treatment for meningioma.
Overview
FDG PET has a structural limitation in the brain: normal grey matter has high baseline glucose uptake, so FDG contrast between tumour and healthy brain tissue is poor, unlike its performance in most body cancers. This drove development from the 1980s onward of radiolabelled amino acid tracers, principally 11C-methionine and later 18F-FET, which exploit the increased amino acid transport of tumour cells against a low physiological background in normal brain.
These tracers were gradually adopted into formal guidance: the PET-RANO working group and EANO published evidence-based recommendations for PET imaging in gliomas in 2016, followed by the joint EANM/EANO/RANO/SNMMI practice guideline (version 1.0) for glioma PET imaging with radiolabelled amino acids and FDG, published in 2019, standardising acquisition and interpretation (for example, a tumour-to-brain ratio threshold of 1.6-1.8 for 18F-FET). An updated RANO/EANO policy review in 2025 strengthened several of these recommendations, including for delineating tumour extent and distinguishing recurrence from treatment-related change.
A parallel and largely separate strand targets meningioma, a tumour that (unlike most gliomas) reliably overexpresses somatostatin receptor 2 (SSTR2). Rachinger et al. (2015) showed that 68Ga-DOTATATE PET uptake correlates with SSTR2 expression and outperforms MRI sensitivity (90% vs 79%) for discriminating meningioma from tumour-free tissue, and it is now used for surgical and radiotherapy planning, particularly at the skull base. Because meningioma expresses the same target as neuroendocrine tumours, it has become a candidate for the same theranostic pairing: a phase 1/2 trial of the alpha emitter 225Ac-DOTATATE (RYZ101) in progressive or recurrent intracranial meningioma opened at Ohio State, testing whether the SSTR theranostic model developed for neuroendocrine tumours extends into neuro-oncology.
- 1980s-1990shistoric
FDG's limits in the brain drive amino acid PET
FDG PET is limited in neuro-oncology by high physiological glucose uptake in normal grey matter, which reduces tumour-to-background contrast. This drives clinical development of radiolabelled amino acid tracers, principally 11C-methionine, which show much better contrast against normal brain from the 1980s onward.
- 2000s-2016historic
18F-FET and the first evidence-based PET guidance for glioma
O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET), an 18F-labelled amino acid tracer with a longer half-life than 11C-methionine, is adopted widely in Europe through the 2000s and 2010s. The PET-RANO working group and EANO publish the first evidence-based recommendations for the clinical use of PET imaging in gliomas in Neuro-Oncology in 2016.
- 2015historic
68Ga-DOTATATE PET for meningioma
Rachinger et al. show, using spatially precise neuronavigated tissue sampling during surgery, that 68Ga-DOTATATE PET uptake correlates with SSTR2 expression and detects meningioma tissue with higher sensitivity than MRI (90% vs 79%), establishing SSTR2 PET as a tool for meningioma delineation, particularly in the skull base and after treatment.
- 2019-2025current
Joint practice guidelines standardise glioma PET
The joint EANM/EANO/RANO/SNMMI practice guideline (version 1.0) for imaging gliomas with PET using radiolabelled amino acids and FDG is published in 2019, standardising acquisition protocols and uptake thresholds (for example, an 18F-FET tumour-to-brain ratio of 1.6-1.8). An updated RANO/EANO policy review in 2025 strengthens the recommendation level for several uses, including delineating glioma extent and distinguishing recurrence from treatment-related change.
- 2020-2026current
68Ga-DOTATATE PET in routine meningioma management
SSTR2 PET with 68Ga-DOTATATE or DOTATOC becomes an established adjunct to MRI for meningioma treatment planning, particularly for delineating disease extent at the skull base, detecting bony invasion, and distinguishing residual tumour from post-surgical or post-radiation change.
- 2025-2028emerging
Emerging: SSTR2 theranostics extends into meningioma therapy
A phase 1/2 trial of the alpha emitter 225Ac-DOTATATE (RYZ101) for progressive or recurrent intracranial meningioma (WHO grades 1-3) opens at Ohio State, using 68Ga-DOTATATE PET to select and follow patients, testing whether the diagnostic-therapeutic SSTR2 pairing developed for neuroendocrine tumours can extend into a tumour type managed mainly by surgery and radiotherapy.
- 2028+speculative
Speculative: broader receptor and alpha-emitter use in brain tumours
If SSTR2 theranostics in meningioma shows benefit, other brain and skull-base tumours with a defined receptor target could follow the same diagnostic-therapeutic pairing, and locoregional alpha-emitter delivery (for example convection-enhanced delivery of astatine-211 conjugates, under early investigation for glioma) could extend targeted radiotherapy to tumours where systemic dosing is limited by the blood-brain barrier.
Probability ranges are named estimates that the claim is borne out on roughly a five-year horizon. They are meant to be argued with: propose a revision with your name and reasoning via a pull request to src/data/confidence.ts.
What to watch
Readouts, decisions and registry completion dates ahead. Each date is quoted from its source, not inferred; a missing date means no source states one.
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Story
topFDG's limits in the brain drive amino acid PET
FDG PET is limited in neuro-oncology by high physiological glucose uptake in normal grey matter, which reduces tumour-to-background contrast. This drives clinical development of radiolabelled amino acid tracers, principally 11C-methionine, which show much better contrast against normal brain from the 1980s onward.
FDG PET is the standard PET scan. A radioactive sugar shows which tissues are burning glucose fast, which most cancers do.
Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions.
18F-FET and the first evidence-based PET guidance for glioma
O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET), an 18F-labelled amino acid tracer with a longer half-life than 11C-methionine, is adopted widely in Europe through the 2000s and 2010s. The PET-RANO working group and EANO publish the first evidence-based recommendations for the clinical use of PET imaging in gliomas in Neuro-Oncology in 2016.
68Ga-DOTATATE PET for meningioma
Rachinger et al. show, using spatially precise neuronavigated tissue sampling during surgery, that 68Ga-DOTATATE PET uptake correlates with SSTR2 expression and detects meningioma tissue with higher sensitivity than MRI (90% vs 79%), establishing SSTR2 PET as a tool for meningioma delineation, particularly in the skull base and after treatment.
Meningiomas grow from the membranes covering the brain and spinal cord rather than from the brain itself. Most are slow and benign and are either watched or removed; radiotherapy or radiosurgery treats what surgery cannot reach or what grows back, and no drug has yet been approved for them.
Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care.
The PET scan for neuroendocrine tumours that finds far more disease than older scans and confirms eligibility for lutetium radioligand therapy (the theranostic pair).
Joint practice guidelines standardise glioma PET
The joint EANM/EANO/RANO/SNMMI practice guideline (version 1.0) for imaging gliomas with PET using radiolabelled amino acids and FDG is published in 2019, standardising acquisition protocols and uptake thresholds (for example, an 18F-FET tumour-to-brain ratio of 1.6-1.8). An updated RANO/EANO policy review in 2025 strengthens the recommendation level for several uses, including delineating glioma extent and distinguishing recurrence from treatment-related change.
68Ga-DOTATATE PET in routine meningioma management
SSTR2 PET with 68Ga-DOTATATE or DOTATOC becomes an established adjunct to MRI for meningioma treatment planning, particularly for delineating disease extent at the skull base, detecting bony invasion, and distinguishing residual tumour from post-surgical or post-radiation change.
Meningiomas grow from the membranes covering the brain and spinal cord rather than from the brain itself. Most are slow and benign and are either watched or removed; radiotherapy or radiosurgery treats what surgery cannot reach or what grows back, and no drug has yet been approved for them.
Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care.
Emerging: SSTR2 theranostics extends into meningioma therapy
A phase 1/2 trial of the alpha emitter 225Ac-DOTATATE (RYZ101) for progressive or recurrent intracranial meningioma (WHO grades 1-3) opens at Ohio State, using 68Ga-DOTATATE PET to select and follow patients, testing whether the diagnostic-therapeutic SSTR2 pairing developed for neuroendocrine tumours can extend into a tumour type managed mainly by surgery and radiotherapy.
Speculative: broader receptor and alpha-emitter use in brain tumours
If SSTR2 theranostics in meningioma shows benefit, other brain and skull-base tumours with a defined receptor target could follow the same diagnostic-therapeutic pairing, and locoregional alpha-emitter delivery (for example convection-enhanced delivery of astatine-211 conjugates, under early investigation for glioma) could extend targeted radiotherapy to tumours where systemic dosing is limited by the blood-brain barrier.
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