Mechanism 03 of 16

Amino-acid and amine transport

These tracers borrow the transporters that supply protein synthesis and noradrenaline recycling. Their advantage over FDG is not affinity — it is that normal brain and normal prostate are quiet on these doors.

Cortex is the reason this family exists. Normal grey matter is so FDG-avid that a glioma can vanish into background, whereas LAT1 traffic in normal brain is low — so methionine and FET show tumour extent, recurrence versus radiation necrosis, and a biopsy target that FDG cannot.

Note the difference in what happens after transport. Methionine is incorporated into protein; FET and fluciclovine are not metabolised at all, so their signal is pure transport and it washes out — which is why fluciclovine is imaged within minutes and why FET is read from a dynamic curve rather than a single frame. MIBG and FDOPA go further: they are handled like the neurotransmitters they resemble and end up stored in vesicles.

tracer in transitstored / metabolisedtransporter or enzyme

Two doors, three fates. Fluciclovine and FET are carried in and carried straight back out — transport is the whole signal, so timing is everything. FDOPA is decarboxylated by AADC into F-18 dopamine and packed away. MIBG is mistaken for noradrenaline by uptake-1 and stored in neurosecretory granules — which is exactly why the drugs that block uptake-1 destroy the study.

The agents

F-18 fluciclovineAxumin

PET

F-18 · t½ 110 min · synthetic leucine analogue

Handle: ASCT2 and LAT1 amino-acid transporters
Trapping: Transported into the cell and not incorporated into protein. Retention is transport-driven and transient, so imaging starts 3–5 minutes after injection.
Use: Biochemically recurrent prostate cancer.
Pitfall: Its real strength is minimal urinary excretion, which keeps the prostate bed and pelvis clean. But inflammatory nodes, prostatitis and marrow take it up, and PSMA PET has largely superseded it on accuracy.

C-11 methionine—

PET

C-11 · t½ 20.4 min · on-site cyclotron required

Handle: LAT1, then incorporation into protein
Trapping: Transported and then built into protein — a genuine synthesis marker. Normal cortex uptake is low, so tumour-to-background contrast in brain far exceeds FDG.
Use: Glioma extent, recurrence versus radiation necrosis, biopsy and radiotherapy target definition.
Pitfall: The 20-minute half-life confines it to cyclotron sites. Macrophages and inflammation take it up, so post-treatment change can still mislead. Pituitary and salivary uptake is physiologic.

F-18 FETfluoroethyltyrosine

PET

F-18 · t½ 110 min · long used in Europe; FDA-approved Sep 2026 (Pixclara)

Handle: LAT1/LAT2
Trapping: Transported, not incorporated into protein. The information is in the dynamic curve: an early peak with washout suggests high grade, a steadily rising curve suggests low grade.
Use: Glioma grading and delineation, recurrence versus treatment effect; the distributable alternative to methionine.
Pitfall: Requires a dynamic acquisition to exploit the kinetics — a single static frame throws away most of the diagnostic content.

F-18 FDOPA—

PET

F-18 · t½ 110 min

Handle: LAT1 transport, then aromatic L-amino acid decarboxylase
Trapping: Transported in, decarboxylated to F-18 dopamine, and stored in vesicles — a transport step and a trapping step in series.
Use: Presynaptic nigrostriatal integrity, neuroendocrine tumours, congenital hyperinsulinism (focal versus diffuse disease), glioma.
Pitfall: Carbidopa premedication blocks peripheral AADC, raising brain and tumour uptake and lowering physiologic pancreatic background (useful for adult insulinoma); it is not recommended for congenital hyperinsulinism, where it can mask the focal lesion. Intense physiologic pancreatic, basal ganglia and biliary activity.

I-123 / I-131 MIBGiobenguane · AdreView, Azedra

SPECT / planar

I-123 · t½ 13.2 h · 159 keV γ · I-131 form is therapeutic

Handle: Uptake-1, the noradrenaline transporter (NET)
Trapping: A guanethidine analogue resembling noradrenaline. Taken into chromaffin and sympathetic neuronal cells by NET, then stored in neurosecretory granules.
Use: Phaeochromocytoma and paraganglioma, neuroblastoma (including therapy), cardiac sympathetic innervation — the heart-to-mediastinum ratio in heart failure and in Lewy body disease.
Pitfall: A long list of drugs blocks uptake-1 and must be withheld: tricyclics, labetalol and other combined blockers, sympathomimetics including decongestants, cocaine, reserpine. Thyroid blockade with SSKI or perchlorate is mandatory. Physiologic liver, salivary, myocardial and bladder activity; brown fat in children.

← 02Ion mimicry and active transport 04 →Chemisorption onto bone mineral IndexAll 16 mechanisms