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

Clin Cancer Res. 2020 Oct 1;26(19):5178-5187. doi: 10.1158/1078-0432.CCR-19-3704. Epub 2020 May 4.


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-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.

Experimental design: 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.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Benzodioxoles
  • HSP90 Heat-Shock Proteins
  • Iodine Radioisotopes
  • Iodine-124
  • Purines
  • 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-