First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer

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. Schoder, Josef J. Fox, Hanwen ZhangGabriela Chiosis, Jason S. Lewis, Steven M. Larson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Purpose: 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-inhuman 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. Experimental Design: Adult patients with cancer (n ¼ 30) received 124I-PU-H71 tracer (20112 MBq, <25 mg) intravenous bolus followed by PET/CT scans and blood radioassays.

Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)5178-5187
Number of pages10
JournalClinical Cancer Research
Issue number19
StatePublished - Oct 1 2020


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