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Epichaperome-targeted myocardial imaging by I-PU-H71 PET. | LitMetric

Background: The small molecule radiotracer I-PU-H71 is an imaging biomarker of epichaperome formation. The tracer has been established to localize in tissues under chronic stress, specifically in cancer cells and neurodegenerative brain cells. A first-in-human imaging trial using positron emission tomography (PET) in cancer patients revealed unexpected tracer accumulation in the myocardium.

Purpose: To describe human I-PU-H71 myocardial biodistribution and pharmacokinetics in a series of cancer patients with no history of cardiovascular disease.

Methods: 25 cancer patients (age 22-75 years, M:F - 7:18) with no history of cardiovascular disease received intravenous injections with microdose I-PU-H71 while at rest, followed by dynamic and gated/non-gated PET image data acquisitions. Region-of-interest (ROI) analysis of left ventricular myocardium (LVmyo) and background left atrium quantified tracer concentrations as standardized uptake value (SUV) and uptake ratios. Kinetic rate constants were evaluated by a two-tissue compartment model.

Results: Myocardial accumulation of I-PU-H71 was prominent in all patients, with median LVmyo SUVmean (interquartile range, IQR) of 2.8 (IQR, 2.13-3.29), 2.5 (IQR, 1.94-2.98), 2.4 (IQR, 1.73-3.31) and 1.0 (IQR, 0.61-2.45), and median LVmyo/blood-pool ratios of 1.9 (IQR, 1.57-2.38), 2.0 (IQR, 1.53-2.32), 3.6 (IQR, 2.91-4.06) and 3.9 (IQR, 2.62-5.08) at 1-9 min, 14-23 min, 3-4 h and 21-25 h, respectively on non-gated PET images. Myocardium showed peak uptake within 2 min post-injection, with sustained myocardial tracer-concentration at 4 h post-injection. Pharmacokinetic modeling revealed median K = 0.45 ml/min/g (IQR, 0.38-0.62); k = 0.47 min (IQR, 0.27-0.71); k = 0.16 min (IQR, 0.09-0.26); and k = 0.0038 min (IQR, 0.0015-0.0057). Regional assessment demonstrated essentially uniform tracer uptake in LV and myocardial segments; with normal LVEF in all patients (mean 57.7 ± 3.5%); and no patients suffered cardiac events over subsequent 12-month period.

Conclusion: Our study finds human myocardial epichaperome expression, as quantified by I-PU-H71 PET. Our data indicates PU-H71 PET merits further study as a myocardial epichaperome biomarker, with potential application in drug development, possibly as a biomarker in subclinical cardiac dysfunction.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810128PMC
http://dx.doi.org/10.1007/s40336-024-00658-9DOI Listing

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