Evaluation of [18F]MFPBG: a novel automatically radiolabeled probe for NET PET imaging

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Cardiology

Background:

• Cardiac sympathetic nerve imaging is vital for sudden death risk stratification in heart failure.
• Conventional SPECT imaging with [123I]MIBG has limitations in resolution and quantification.
• Existing PET probes face challenges like high liver uptake and low radiolabeling efficiency.

Purpose of the Study:

• To develop and evaluate a novel norepinephrine transporter (NET) PET probe, [18F]MFPBG, for cardiac sympathetic nerve imaging.
• To assess the probe's radiolabeling efficiency, stability, and biodistribution.
• To determine the probe's potential for clinical translation in heart failure risk stratification.

Main Methods:

• Automated radiolabeling module was used for [18F]MFPBG synthesis.
• Radiochemical yield, purity, and stability were determined.
• Biodistribution studies were conducted in ICR mice and Bama miniature pigs, including assessment of cardiac uptake and heart-to-liver ratios.
• Pharmacological blockade with imipramine was used to confirm NET-mediated uptake.

Main Results:

• [18F]MFPBG achieved a decay-corrected radiochemical yield of 15.14±2.57% with >95% purity and stability for 4 hours.
• In mice, cardiac uptake was 9.34±0.73 %ID/g at 5 min, with a heart-to-liver ratio of 3.99±0.15, remaining high at 120 min.
• In pigs, imipramine significantly reduced cardiac uptake (P < 0.001), confirming NET-mediated targeting.

Conclusions:

• [18F]MFPBG exhibits NET-mediated uptake and stable cardiac retention.
• The probe demonstrates low background noise and suitability for automated radiolabeling.
• [18F]MFPBG is a promising agent for cardiac sympathetic nerve imaging, warranting further preclinical validation for clinical translatability.