Dynamic [¹⁸F]Fluoroleucine PET Detects Impaired Cardiac Leucine Uptake Before Hypertensive Left Ventricular...

Left ventricular hypertrophy (LVH) is a major complication of chronic hypertension and an independent cardiovascular risk factor. No clinically validated markers exist to identify hypertensive individuals at risk for developing LVH. We previously described metabolic changes preceding LVH in hypertensive rat hearts, including alterations in branched-chain amino acid (BCAA) metabolism. This study investigated whether impaired cardiac leucine uptake, measured with dynamic 5-[¹⁸F]fluoroleucine ([¹⁸F]FLE) PET imaging, could serve as in vivo marker for hypertension-induced LVH development.

[¹⁸F]FLE was synthesized following established radiochemistry protocols and dynamic [¹⁸F]FLE-PET/CT imaging was performed in 3-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats (n = 4/group). Cardiac MR (CMR) imaging enabled structural co-registration. A dual-output reversible two-tissue compartment model with spill-over and partial volume corrections quantified the first-pass rate constant (K₁) and total distribution volume (V_t). L-type amino acid transporter 1 (LAT1/SLC7A5) protein expression and branched-chain keto acid dehydrogenase (BCKDH) phosphorylation status were assessed by immunoblotting of heart tissue.

SHR demonstrated markedly lower K₁ and V_t compared with WKY rats, consistent with reduced cardiac leucine uptake. Simultaneously, LAT1 expression was significantly reduced in SHR hearts. Elevated BCKDH phosphorylation at Ser293 suggested impaired BCAA catabolism.

Dynamic cardiac [¹⁸F]FLE-PET detects decreased leucine uptake in hypertensive rat hearts at 3 months of age, before LVH is established at 5 months. Impaired cardiac leucine uptake may thus serve as an early cardiometabolic biomarker to identify hypertensive patients at risk for LVH progression.