Progress in first-in-human trial of Hsp90-targeted PET imaging in cancer patients

Objectives Provide an update on PET microdose clinical trial of I-124 PUH71, a radiolabeled heat shock protein 90 (Hsp90) inhibitor, in an expanded cohort of cancer types.

Methods Trial performed under IRB-approved protocol and US FDA-approved IND. Main eligibility criteria: >18 years; evaluable tumors on clinical imaging; serum liver and renal indices within specified range; no hyperthyroidism. I-124 PUH71 tracer microdose injected peripheral IV. PET-CT scans obtained at multiple time-points up to 7-8 days, post-injection. Serial blood sampling for activity and metabolite assays. MIRD formalism and OLINDA software used for dosimetry analyses of PET-derived and blood time-activity data.

Results 20 patients to-date, with breast (n=9), lymphoma (NHL n=4; Hodgkin=1), pancreatic (n=2), neuroblastoma (n=2), fallopian tube (n=1), and prostate (n=1) cancers. PUH71 tracer safe in all 20 patients. Learned optimal PET protocol for tumor imaging. Variety of histological types of tumors evident on PUH71 PET (Suppl Fig. 1). PUH71 biodistribution suggests other potential PET clinical applications.

Conclusions Our expanded trial data demonstrates the feasibility of detecting tumors in human subjects by Hsp90-targeted PET in a wider variety of human cancers than we previously reported. Further development of I-124 PUH71 as a first-of-its-kind Hsp90-targeted PET imaging agent ongoing, including new clinical applications.

Research Support Clinical trial supported by Samus Therapeutics; MSKCC Breast Cancer Research Fund 3 Preclinical development supported by ICMIC P50 CA 086438; SAIRP grant R24 CA83084; and the Cyclotron-Radiochemistry Core of MSKCC.