Epichaperome-targeted myocardial imaging by ¹²⁴I-PU-H71 PET

Area of Science:

• Nuclear medicine
• Molecular imaging
• Cardiovascular research

Background:

• ¹²⁴I-PU-H71 is a small molecule radiotracer and imaging biomarker for epichaperome formation.
• It is known to localize in tissues under chronic stress, including cancer and neurodegenerative cells.
• Unexpected myocardial accumulation was observed in a prior human trial using ¹²⁴I-PU-H71 PET in cancer patients.

Purpose of the Study:

• To characterize the myocardial biodistribution and pharmacokinetics of ¹²⁴I-PU-H71 in humans.
• To assess myocardial uptake in cancer patients without pre-existing cardiovascular disease.

Main Methods:

• 25 cancer patients without cardiovascular disease history underwent intravenous microdose ¹²⁴I-PU-H71 injection.
• Dynamic and gated/non-gated positron emission tomography (PET) imaging was performed.
• Region-of-interest analysis quantified tracer concentration (SUV, uptake ratios), and kinetic modeling was applied.

Main Results:

• Prominent myocardial accumulation of ¹²⁴I-PU-H71 was observed in all patients.
• Peak myocardial uptake occurred within 2 minutes, with sustained levels at 4 hours post-injection.
• Pharmacokinetic modeling provided rate constants (K1, k2, k3, k4), and uniform tracer uptake was noted in myocardial segments with normal cardiac function.

Conclusions:

• This study demonstrates human myocardial epichaperome expression quantifiable by ¹²⁴I-PU-H71 PET.
• ¹²⁴I-PU-H71 PET shows promise as a myocardial epichaperome biomarker.
• Potential applications include drug development and as a biomarker for subclinical cardiac dysfunction.