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

• Published in: Clinical cancer research 2020-10, Vol.26 (19), p.5178-5187
• Main Authors: Dunphy, Mark P S, Pressl, Christina, Pillarsetty, Nagavarakishore, Grkovski, Milan, Modi, Shanu, Jhaveri, Komal, Norton, Larry, Beattie, Bradley J, Zanzonico, Pat B, Zatorska, Danuta, Taldone, Tony, Ochiana, Stefan O, Uddin, Mohammad M, Burnazi, Eva M, Lyashchenko, Serge K, Hudis, Clifford A, Bromberg, Jacqueline, Schöder, Heiko M, Fox, Josef J, Zhang, Hanwen, Chiosis, Gabriela, Lewis, Jason S, Larson, Steven M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Benzodioxoles - administration & dosage; Benzodioxoles - adverse effects; Cell Line, Tumor; Cell Proliferation - drug effects; Female; HSP90 Heat-Shock Proteins - genetics; Humans; Iodine Radioisotopes - administration & dosage; Male; Middle Aged; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Positron Emission Tomography Computed Tomography - methods; Purines - administration & dosage; Purines - adverse effects; Tissue Distribution - radiation effects
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-3704

I-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 I-PU-H71 for PET to study biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. Adult patients with cancer ( = 30) received I-PU-H71 tracer (201±12 MBq,