American Association for Cancer Research
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Supplemental Figure 1 from First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer

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posted on 2023-03-31, 22:12 authored by Mark P.S. Dunphy, Christina Pressl, Nagavarakishore Pillarsetty, Milan Grkovski, Shanu Modi, Komal Jhaveri, Larry Norton, Bradley J. Beattie, Pat B. Zanzonico, Danuta Zatorska, Tony Taldone, Stefan O. Ochiana, Mohammad M. Uddin, Eva M. Burnazi, Serge K. Lyashchenko, Clifford A. Hudis, Jacqueline Bromberg, Heiko M. Schöder, Josef J. Fox, Hanwen Zhang, Gabriela Chiosis, Jason S. Lewis, Steven M. Larson

Supplemental Figure 1. Tumor retention of PU-H71 tracer varied considerably between patients. Tumor retention expressed as tumor:bloodpool SUV ratio (y-axis) measured on PET at 4 and 24 hours post tracer-injection.






124I-PU-H71 is an investigational first-in-class radiologic agent specific for imaging tumor epichaperome formations. The intracellular epichaperome forms under cellular stress and is a clinically validated oncotherapeutic target. We conducted a first-in-human study of microdose 124I-PU-H71 for PET to study in vivo biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. Adult patients with cancer (n = 30) received 124I-PU-H71 tracer (201±12 MBq, <25 μg) intravenous bolus followed by PET/CT scans and blood radioassays. 124I-PU-H71 PET detected tumors of different cancer types (breast, lymphoma, neuroblastoma, genitourinary, gynecologic, sarcoma, and pancreas). 124I-PU-H71 was retained by tumors for several days while it cleared rapidly from bones, healthy soft tissues, and blood. Radiation dosimetry is favorable and patients suffered no adverse effects. Our first-in-human results demonstrate the safety and feasibility of noninvasive in vivo detection of tumor epichaperomes using 124I-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics.