Sonia Mahajan, Milan Grkovski, Kevin D Staton, Susana Ravassa, Kwaku Domfe, H William Strauss, John L Humm, Pat B Zanzonico, Bradley J Beattie, Insang Cho, Eva M Burnazi, Josef J Fox, Heiko Schöder, Joseph R Osborne, Trisha Youn, Komal Jhaveri, Gabriela Chiosis, Mark P Dunphy
{"title":"经124I-PU-H71 PET显像的表色素靶向心肌显像。","authors":"Sonia Mahajan, Milan Grkovski, Kevin D Staton, Susana Ravassa, Kwaku Domfe, H William Strauss, John L Humm, Pat B Zanzonico, Bradley J Beattie, Insang Cho, Eva M Burnazi, Josef J Fox, Heiko Schöder, Joseph R Osborne, Trisha Youn, Komal Jhaveri, Gabriela Chiosis, Mark P Dunphy","doi":"10.1007/s40336-024-00658-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The small molecule radiotracer <sup>124</sup>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.</p><p><strong>Purpose: </strong>To describe human <sup>124</sup>I-PU-H71 myocardial biodistribution and pharmacokinetics in a series of cancer patients with no history of cardiovascular disease.</p><p><strong>Methods: </strong>25 cancer patients (age 22-75 years, M:F - 7:18) with no history of cardiovascular disease received intravenous injections with microdose <sup>124</sup>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.</p><p><strong>Results: </strong>Myocardial accumulation of <sup>124</sup>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<sub>1</sub> = 0.45 ml/min/g (IQR, 0.38-0.62); k<sub>2</sub> = 0.47 min<sup>- 1</sup> (IQR, 0.27-0.71); k<sub>3</sub> = 0.16 min<sup>- 1</sup> (IQR, 0.09-0.26); and k<sub>4</sub> = 0.0038 min<sup>- 1</sup> (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.</p><p><strong>Conclusion: </strong>Our study finds human myocardial epichaperome expression, as quantified by <sup>124</sup>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.</p>","PeriodicalId":48600,"journal":{"name":"Clinical and Translational Imaging","volume":"12 6","pages":"619-627"},"PeriodicalIF":2.3000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810128/pdf/","citationCount":"0","resultStr":"{\"title\":\"Epichaperome-targeted myocardial imaging by <sup>124</sup>I-PU-H71 PET.\",\"authors\":\"Sonia Mahajan, Milan Grkovski, Kevin D Staton, Susana Ravassa, Kwaku Domfe, H William Strauss, John L Humm, Pat B Zanzonico, Bradley J Beattie, Insang Cho, Eva M Burnazi, Josef J Fox, Heiko Schöder, Joseph R Osborne, Trisha Youn, Komal Jhaveri, Gabriela Chiosis, Mark P Dunphy\",\"doi\":\"10.1007/s40336-024-00658-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The small molecule radiotracer <sup>124</sup>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.</p><p><strong>Purpose: </strong>To describe human <sup>124</sup>I-PU-H71 myocardial biodistribution and pharmacokinetics in a series of cancer patients with no history of cardiovascular disease.</p><p><strong>Methods: </strong>25 cancer patients (age 22-75 years, M:F - 7:18) with no history of cardiovascular disease received intravenous injections with microdose <sup>124</sup>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.</p><p><strong>Results: </strong>Myocardial accumulation of <sup>124</sup>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<sub>1</sub> = 0.45 ml/min/g (IQR, 0.38-0.62); k<sub>2</sub> = 0.47 min<sup>- 1</sup> (IQR, 0.27-0.71); k<sub>3</sub> = 0.16 min<sup>- 1</sup> (IQR, 0.09-0.26); and k<sub>4</sub> = 0.0038 min<sup>- 1</sup> (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.</p><p><strong>Conclusion: </strong>Our study finds human myocardial epichaperome expression, as quantified by <sup>124</sup>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.</p>\",\"PeriodicalId\":48600,\"journal\":{\"name\":\"Clinical and Translational Imaging\",\"volume\":\"12 6\",\"pages\":\"619-627\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810128/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40336-024-00658-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40336-024-00658-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/20 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Epichaperome-targeted myocardial imaging by 124I-PU-H71 PET.
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.
期刊介绍：
Clinical and Translational Imaging is an international journal that publishes timely, up-to-date summaries on clinical practice and translational research and clinical applications of approved and experimental radiopharmaceuticals for diagnostic and therapeutic purposes. Coverage includes such topics as advanced preclinical evidence in the fields of physics, dosimetry, radiation biology and radiopharmacy with relevance to applications in human subjects. The journal benefits a readership of nuclear medicine practitioners and allied professionals involved in molecular imaging and therapy.
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