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

Abstract

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 <i>in vivo</i> biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. Adult patients with cancer (<i>n</i> = 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 <i>in vivo</i> detection of tumor epichaperomes using ¹²⁴I-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics.