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Updated: May 26, 2026
High-Resolution Cardiac Positron Emission Tomography/Computed Tomography for Small Animals
Published on: December 16, 2022
Dynamic [ 18 F]Fluoroleucine PET Detects Impaired Cardiac Leucine Uptake Before Hypertensive Left Ventricular
Insights
Hypertension impairs cardiac leucine uptake in rats before left ventricular hypertrophy (LVH) develops. Positron emission tomography imaging can detect this metabolic change, offering a potential marker for early detection of cardiovascular risk.
Area of Science:
- Cardiovascular Medicine
- Nuclear Medicine
- Biochemistry
Background:
- Left ventricular hypertrophy (LVH) is a significant complication of hypertension, increasing cardiovascular morbidity and mortality.
- Currently, no validated clinical markers exist to identify hypertensive individuals at risk for LVH.
- Previous studies identified metabolic changes, including in branched-chain amino acid (BCAA) metabolism, preceding LVH in hypertensive rat hearts.
Purpose of the Study:
- To investigate if cardiac leucine uptake, measured by dynamic 5-[18F]fluoroleucine positron emission tomography-computed tomography ([18F]FLE-PET/CT), is impaired in hypertension.
- To determine if [18F]FLE-PET/CT can serve as an in vivo marker for hypertension-induced LVH development.
Main Methods:
- Dynamic [18F]FLE-PET/CT imaging was performed on spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.
- Cardiac magnetic resonance (CMR) imaging was used for structural co-registration.
- A compartment model quantified [18F]FLE uptake kinetics; LAT1 and BCKDH phosphorylation were assessed via immunoblotting.
Main Results:
- SHR exhibited significantly lower cardiac leucine uptake rates (K1) and distribution volumes (Vt) compared to WKY rats.
- Reduced expression of L-type amino acid transporter 1 (LAT1) was observed in SHR hearts.
- Elevated BCKDH phosphorylation indicated impaired BCAA catabolism in SHR.
Conclusions:
- Dynamic cardiac [18F]FLE-PET imaging detects reduced leucine uptake in hypertensive rat hearts before LVH onset.
- Decreased cardiac leucine uptake may indicate impaired BCAA metabolism and serve as an early in vivo marker of cardiometabolic dysfunction preceding LVH.
- This imaging approach has translational potential for identifying hypertensive patients at risk for LVH progression.
Purpose:
Left ventricular hypertrophy (LVH) is a major complication of chronic hypertension and an independent risk factor for cardiovascular morbidity and mortality. There are currently no clinically validated markers available to identify hypertensive individuals at risk for developing LVH. In hearts of hypertensive rats, we previously described metabolic changes that precede LVH development, including in branched-chain amino acid (BCAA) metabolism. This study investigated whether cardiac leucine uptake, measured with dynamic 5-[ 18 F]fluoroleucine positron emission tomography-computed tomography ([ 18 F]FLE-PET/CT), was impaired and could serve as an in vivo marker for hypertension-induced LVH development.
Procedures:
We synthesized [ 18 F]FLE following established radiochemistry protocols and performed dynamic [ 18 F]FLE-PET/CT imaging in 3-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats (n = 4 per group). Cardiac magnetic resonance (CMR) imaging was conducted on the same animals for structural co-registration. A dual-output reversible two-tissue compartment model with spill-over (SP) and partial volume (PV) corrections was developed to quantify the first-pass rate constant (K 1 ) and total distribution volume (V t = K 1 /k 2 ) for [ 18 F]FLE. Protein expression of L-type amino acid transporter 1 (LAT1) and branched-chain keto acid dehydrogenase (BCKDH) phosphorylation status were assessed by immunoblotting of isolated heart tissue.
Results:
SHR demonstrated markedly lower first-pass leucine uptake rates (K 1 ) and total distribution volumes (V t ) compared with WKY rats, consistent with reduced cardiac BCAA uptake. Concurrently, LAT1 (SLC7A5) expression was significantly reduced in SHR hearts compatible with decreased leucine uptake. Elevated BCKDH phosphorylation at Ser293 in SHR hearts indicated diminished BCKDH enzymatic activity and impaired BCAA catabolism.
Conclusions:
Dynamic cardiac [ 18 F]FLE-PET imaging successfully detects decreased leucine uptake in hypertensive rat hearts at 3 months of age, before LVH is established at 5 months. Reduced cardiac leucine uptake may thus serve as a surrogate marker for impaired cardiac BCAA metabolism and early in vivo indicator of cardiometabolic dysfunction that precedes LVH. The imaging approach holds translational potential for identifying hypertensive patients at risk for LVH progression.
