First-in-human trial of epichaperome-targeted PET in patients with cancer Journal Article
| Authors: | Dunphy, M. P. S.; Pressl, C.; Pillarsetty, N.; Grkovski, M.; Modi, S.; Jhaveri, K.; Norton, L.; Beattie, B. J.; Zanzonico, P. B.; Zatorska, D.; Taldone, T.; Ochiana, S. O.; Uddin, M. M.; Burnazi, E. M.; Lyashchenko, S. K.; Hudis, C. A.; Bromberg, J.; Schöder, H. M.; Fox, J. J.; Zhang, H. W.; Chiosis, G.; Lewis, J. S.; Larson, S. M. |
| Article Title: | First-in-human trial of epichaperome-targeted PET in patients with cancer |
| Abstract: | Purpose: I-124-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 I-124-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 I-124-PU-H71 tracer (201 + 12 MBq, <25 mu g) intravenous bolus followed by PET/CT scans and blood radioassays. Results: I-124-PU-H71 PET detected tumors of different cancer types (breast, lymphoma, neuroblastoma, genitourinary, gynecologic, sarcoma, and pancreas). I-124-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 I-124-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics. |
| Keywords: | prostate-cancer; inhibition; phase-i; pu-h71; 17-allylamino-17-demethoxygeldanamycin; androgen-receptor |
| Journal Title: | Clinical Cancer Research |
| Volume: | 26 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2020-10-01 |
| Start Page: | 5178 |
| End Page: | 5187 |
| Language: | English |
| ACCESSION: | WOS:000576795700017 |
| DOI: | 10.1158/1078-0432.Ccr-19-3704 |
| PROVIDER: | wos |
| PMCID: | PMC7541604 |
| PUBMED: | 32366671 |
| Notes: | Article -- Source: Wos |
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