Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec;12(6):619-627.
doi: 10.1007/s40336-024-00658-9. Epub 2024 Sep 20.

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

Sonia Mahajan  1 , Milan Grkovski  2 , Kevin D Staton  3   4 , Susana Ravassa  5   6 , Kwaku Domfe  7 , H William Strauss  1 , John L Humm  2 , Pat B Zanzonico  2 , Bradley J Beattie  2 , Insang Cho  1 , Eva M Burnazi  3 , Josef J Fox  1 , Heiko Schöder  1 , Joseph R Osborne  8 , Trisha Youn  8   9 , Komal Jhaveri  10 , Gabriela Chiosis  11 , Mark P Dunphy  1
Affiliations

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

Sonia Mahajan et al. Clin Transl Imaging. 2024 Dec.

Abstract

Background: The small molecule radiotracer 124I-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 124I-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 124I-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 124I-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 K1 = 0.45 ml/min/g (IQR, 0.38-0.62); k2 = 0.47 min- 1 (IQR, 0.27-0.71); k3 = 0.16 min- 1 (IQR, 0.09-0.26); and k4 = 0.0038 min- 1 (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 124I-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.

Keywords: Cancer and cardiovascular disease; Iodine-124; Myocardial imaging; PU-H71; Positron-emission tomography.

PubMed Disclaimer

Conflict of interest statement

Competing interests The authors declare no competing interests.

References

    1. Rodina A, Wang T, Yan P, Gomes ED, Dunphy MP, Pillarsetty N et al. (2016) The epichaperome is an integrated chaperome network that facilitates tumour survival. Nature 538(7625):397–401 - PMC - PubMed
    1. Joshi S, Wang T, Araujo TLS, Sharma S, Brodsky JL, Chiosis G (2018) Adapting to stress - chaperome networks in cancer. Nat Rev Cancer 18(9):562–575 - PMC - PubMed
    1. Inda MC, Joshi S, Wang T, Bolaender A, Gandu S, Koren Iii J et al. (2020) The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction. Nat Commun 11(1):319. - PMC - PubMed
    1. Kishinevsky S, Wang T, Rodina A, Chung SY, Xu C, Philip J et al. (2018) HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons. Nat Commun 9(1):4345. - PMC - PubMed
    1. Pillarsetty N, Jhaveri K, Taldone T, Caldas-Lopes E, Punzalan B, Joshi S et al. (2019) Paradigms for Precision Medicine in Epichaperome Cancer Therapy. Cancer Cell 36(5):559–573e7 - PMC - PubMed