F-18-FDG¹⁸F-FDG

Quick Answer

F-18-FDG is a glucose analog transported into cells by GLUT transporters and phosphorylated by hexokinase to FDG-6-phosphate, which is metabolically trapped (not further metabolized). Uptake therefore images glucose metabolism — elevated in most cancers, activated inflammatory cells, and metabolically active myocardium. It is the single most-used PET tracer, spanning oncologic staging/restaging/response, infection/inflammation, cardiac viability and sarcoid, and neurology. Interpretation hinges on preparation (glucose/fasting) and knowing the physiologic-uptake mimics.

Mechanism

FDG follows glucose into the cell via GLUT (GLUT-1/GLUT-3) transporters and is phosphorylated by hexokinase to FDG-6-phosphate. Because the 2-hydroxyl is replaced by fluorine, it is not a substrate for further glycolysis and (in most tissues, which have low glucose-6-phosphatase) is trapped. Trapping is proportional to glucose-metabolic rate — high in proliferating tumor and activated immune cells — and SUV quantifies the trapped fraction over the uptake period. Well-differentiated hepatocellular carcinoma is the instructive exception: retained glucose-6-phosphatase dephosphorylates and clears FDG (hence FDG-low).

Biodistribution

Intense physiologic uptake in brain (obligate glucose user — limits brain-metastasis detection), variable myocardium (diet-dependent), liver/spleen (reference regions), bowel, and renal/ureteric/bladder excretion (FDG is renally excreted, unlike glucose). Variable muscle, brown fat, marrow, lymphoid (Waldeyer), and salivary uptake are the physiologic mimics.

Physics

Clinical Indications

• Oncology: staging, restaging, response, prognosis across FDG-avid cancers; RT planning; occult-primary and paraneoplastic work-up.
• Infection/inflammation: fever of unknown origin, large-vessel vasculitis, spondylodiscitis, vascular-graft/device infection, sarcoidosis activity.
• Cardiac: viability (perfusion–metabolism mismatch) and sarcoid (with dietary suppression).
• Neurology: dementia hypometabolism patterns; epilepsy interictal hypometabolism (limited for brain tumors — high cortical background).

Preparation (Determinative)

• Fast 4–6 h, control glucose (< ~150–200 mg/dL) — hyperglycemia/insulin compete and shift FDG to muscle.
• No strenuous exercise ~24 h; warm, quiet environment (muscle/brown fat/laryngeal uptake).
• Consistent uptake time (~60 min) for valid/serial SUV; hydrate/void.
• Cardiac prep is disease-specific: suppress myocardium for sarcoid, promote it for viability.
• Hold metformin ~24–48 h (per protocol) for abdominal reads.

Interpretation Highlights

• SUV semi-quantifies uptake; reference to liver/blood pool (Deauville/PERCIST).
• FDG-low malignancies exist (lobular breast, mucinous, well-differentiated HCC, some neuroendocrine, low-grade sarcoma) — a normal SUV does not exclude cancer.
• Inflammatory/post-therapy uptake and immunotherapy irAEs mimic disease — respect timing.

Reporting Checklist

• Document glucose, fasting, uptake time, injected activity, and any BAT-reduction measures.
• Attribute physiologic patterns explicitly (brown fat, muscle, thymic rebound, G-CSF marrow, cyclical pelvis).
• Report SUVmax of target lesions; use liver/blood-pool reference for response; keep prep consistent across serial scans.
• Recommend brain MRI where cerebral disease matters (PET insensitive).

Common Pitfalls

• Hyperglycemia degrading tumor conspicuity; metformin bowel uptake.
• Brown fat / muscle / thymic rebound / G-CSF marrow false positives.
• Under-calling FDG-low histologies; over-calling inflammation/irAE.

Board Pearls

FDG is a glucose analog: GLUT transport + hexokinase phosphorylation → metabolic trapping proportional to glucose metabolism (high in cancer/inflammation/active myocardium). Preparation determines the study — fast/control glucose, consistent ~60-min uptake time, and disease-specific cardiac prep (suppress for sarcoid, promote for viability).

FDG-low does not mean benign: lobular/mucinous, well-differentiated HCC (glucose-6-phosphatase clears it), some neuroendocrine, and low-grade tumors are poorly avid. Conversely, inflammation, post-therapy change, and immunotherapy irAEs cause false positives — timing and pattern recognition are essential.

FDG is renally excreted (unlike glucose), so urinary activity obscures the pelvis, and intense cortical brain uptake makes PET insensitive for brain metastases (use MRI). Serial SUV comparison requires matched uptake time, glucose, and reconstruction (EARL harmonization for cross-site work).

Related Pages

• Reference: FDG-PET preparation & physiologic uptake, oncology response criteria (RECIST/PERCIST).
• Applied: FDG PET in oncology and the individual disease pages; pitfalls: Incidental findings on FDG-PET.

Figure / Diagram Suggestions

• A GLUT/hexokinase trapping mechanism cartoon (with the HCC/G6Pase exception).
• A normal biodistribution + physiologic mimics whole-body plate.

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