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Published on: November 12, 2019
First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer
Mark P S Dunphy1, Christina Pressl2, Nagavarakishore Pillarsetty3,4
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. dunphym@mskcc.org.
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.
Insights
The investigational agent 124I-PU-H71 safely images tumor epichaperomes in humans. This first-in-human study shows feasibility for epichaperome-targeted cancer imaging and therapy development.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- The intracellular epichaperome is a validated oncotherapeutic target, forming under cellular stress.
- 124I-PU-H71 is a novel radiologic agent designed for imaging epichaperome formations.
Purpose of the Study:
- To evaluate the safety, biodistribution, pharmacokinetics, and metabolism of microdose 124I-PU-H71 in a first-in-human study.
- To assess the feasibility of in vivo epichaperome-targeted tumor imaging using 124I-PU-H71 and Positron Emission Tomography (PET).
Main Methods:
- A first-in-human study involving 30 adult cancer patients.
- Administration of microdose 124I-PU-H71 tracer (201±12 MBq, <25 μg) via intravenous bolus.
- PET/CT scans and blood radioassays were performed to analyze biodistribution and pharmacokinetics.
Main Results:
- 124I-PU-H71 PET successfully detected tumors across various cancer types, including breast, lymphoma, and sarcoma.
- The agent demonstrated favorable retention in tumors for several days with rapid clearance from healthy tissues and blood.
- Radiation dosimetry was favorable, and no adverse effects were reported by patients.
Conclusions:
- First-in-human results confirm the safety and feasibility of noninvasive in vivo detection of tumor epichaperomes using 124I-PU-H71 PET.
- These findings support the clinical development of PU-H71 and other epichaperome-targeted therapeutics.
- 124I-PU-H71 represents a promising tool for guiding epichaperome-targeted cancer therapies.
