Mitochondrial retention
A lipophilic cation is dragged across two membranes by the steep negative potential inside the mitochondrion and simply sits there. Uptake tracks mitochondrial density — which is why one class of agent images myocardium, parathyroid adenoma and breast tumour.
Sestamibi is passive but not indifferent: it crosses the plasma membrane because it is lipophilic, and concentrates in the matrix because the inner mitochondrial membrane sits at roughly −150 mV. Parathyroid imaging works because oxyphil cells are packed with mitochondria and hold the tracer while thyroid washes out.
Two things then complicate it. P-glycoprotein — the multidrug-resistance pump — actively extrudes sestamibi, so a mitochondria-rich lesion that expresses MDR1 can be falsely negative. And extraction rolls off at high flow, so a stress study underestimates hyperaemia. Flurpiridaz solves the second problem by a different route: it does not rely on potential at all, it binds complex I, with first-pass extraction near 94% and a nearly linear relationship to flow.
The agents
Tc-99m sestamibiMIBI · Cardiolite
SPECT / planarTc-99m · t½ 6.01 h · 140 keV γ · lipophilic monovalent cation
- Handle
- Mitochondrial membrane potential
- Trapping
- Diffuses in passively, then concentrates ~90% within mitochondria under the negative potential. Extraction ~60–65% with marked roll-off at high flow, and minimal redistribution — so rest and stress require separate injections.
- Use
- Myocardial perfusion, parathyroid adenoma (oxyphil cells retain while thyroid washes out on delayed images), scintimammography, MDR phenotyping.
- Pitfall
- Hepatobiliary excretion puts activity next to the inferior wall — wait 30–60 min or give a fatty meal. Breast and diaphragmatic attenuation. Balanced three-vessel disease can look uniformly normal. P-glycoprotein efflux causes false-negative parathyroid and tumour studies.
Tc-99m tetrofosminMyoview
SPECT / planarTc-99m · t½ 6.01 h · lipophilic diphosphine cation
- Handle
- Mitochondrial membrane potential
- Trapping
- Same class as sestamibi with faster hepatic clearance, so imaging can begin sooner.
- Use
- Myocardial perfusion; parathyroid in some protocols.
- Pitfall
- Slightly lower myocardial extraction than sestamibi, so contrast is marginally poorer; the trade is a shorter protocol. Also subject to P-gp efflux.
F-18 flurpiridazFlyrcado
PETF-18 · t½ 110 min · approved September 2024 · pyridaben analogue
- Handle
- Mitochondrial complex I, PSST subunit
- Trapping
- Binds complex I rather than relying on membrane potential. First-pass extraction ~94% with a near-linear flow relationship even at hyperaemic flows — the roll-off that limits sestamibi, rubidium and ammonia is largely gone.
- Use
- PET myocardial perfusion and absolute flow. The 110-minute half-life allows unit-dose delivery without an on-site cyclotron or generator, and — unlike rubidium, and far more practically than ammonia — permits treadmill exercise stress.
- Pitfall
- A new agent: availability, reimbursement and normal-database experience are still expanding. Interpretation of the high-extraction flow curves differs from rubidium, so departmental thresholds need to be re-derived rather than carried over.