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 - Funding Information:
This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748, as well as by NIH grants R01 CA172546, P01 CA186866, R56 AG061869, P50 CA192937, R21 CA167803, and R35 CA232130. Samus Therapeutics Inc., the Jane H. Gordon Breast Cancer Research Fund, the Breast Cancer Research Fund, Susan G. Komen for the Cure, and the Experimental Therapeutics Center of MSK also provided support for this research. We thank Ms. Leah Bassity for editorial assistance. We are indebted to Dr. Rashid Ghani and his MSKCC Radiopharmacy staff, MSKCC Radiology RN Louise Harris, and MSKCC Radiology research team members Tamara Torres, Brian Krichevsky, Alicia Lashley, and Crystal Gansukh for their assistance in conducting the patient studies.
Funding Information:
This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748, as well as by NIH grants R01 CA172546, P01 CA186866, R56 AG061869, P50 CA192937, R21 CA167803, and R35 CA232130. Samus Therapeutics Inc., the Jane H. Gordon Breast Cancer Research Fund, the Breast Cancer Research Fund, Susan G. Komen for the Cure, and the Experimental Therapeutics Center of MSK also provided support for this research. We thank Ms. Leah Bassity for editorial
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 -