TY - JOUR
T1 - First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer
AU - Dunphy, Mark P.S.
AU - Pressl, Christina
AU - Pillarsetty, Nagavarakishore
AU - Grkovski, Milan
AU - Modi, Shanu
AU - Jhaveri, Komal
AU - Norton, Larry
AU - Beattie, Bradley J.
AU - Zanzonico, Pat B.
AU - Zatorska, Danuta
AU - Taldone, Tony
AU - Ochiana, Stefan O.
AU - Uddin, Mohammad M.
AU - Burnazi, Eva M.
AU - Lyashchenko, Serge K.
AU - Hudis, Clifford A.
AU - Bromberg, Jacqueline
AU - Schoder, Heiko M.
AU - Fox, Josef J.
AU - Zhang, Hanwen
AU - Chiosis, Gabriela
AU - Lewis, Jason S.
AU - Larson, Steven M.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097463797&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-3704
DO - 10.1158/1078-0432.CCR-19-3704
M3 - Article
C2 - 32366671
AN - SCOPUS:85097463797
SN - 1078-0432
VL - 26
SP - 5178
EP - 5187
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -