Using 124I-PU-H71 PET imaging to predict intratumoral concentration in patients on a phase I trial of PU-H71.

Abstract

11076 Background: PU-H71 is a Heat Shock Protein 90 inhibitor that can be labeled with 124I without altering its biochemical properties. Intratumoral drug concentration can be calculated based on 124I-PU-H71 (*PU-H71) region of interest analysis and dilution principle. A microdose pilot study has shown uptake of *PU-H71 in a variety of tumors. *PU-H71 PET is currently being used to estimate intratumoral concentrations in subjects on our phase I study. Methods: Patients with previously treated solid tumors or lymphoma are eligible for this phase 1 trial. PU-H71 is given twice-weekly for 2 weeks each 21 days at escalating dose levels. A mix of *PU-H71 and unlabeled PU-H71 is given during cycle 2 followed by serial PET imaging. Patients on the pilot study are administered a microdose of *PU-H71 alone, followed by serial PET scans. Intratumoral PUH-71 concentration is measured directly in optional pre- and post- treatment core needle tumor biopsies (CNB). Results: To date, 13 patients have received PU-H71 on the phase I trial. Of these, 10 have undergone *PU-H71 PET imaging. 4 imaged patients also volunteered for CNBs, with results reported in the table. Of the 10 patients who underwent *PU-H71 imaging in the phase 1 study, 5 also underwent prior *PU-H71 imaging in the microdose pilot. Intratumoral concentrations as calculated in the pilot and phase I studies were in close concordance. Conclusions: *PU-H71 can be used to visualize PU-H71 uptake in a variety of solid tumors and lymphoma, and *PU-H71 PET scans can be used to estimate intratumoral concentrations of PU-H71. Direct intratumoral measurements of PU-H71 correlate reasonably closely with concentrations calculated from *PU-H71 PET imaging. Further refinement of this imaging tool will allow quantitative assessment of PU-H71 uptake in tumors during the ongoing phase I trial. Clinical trial information: NCT01393509. [Table: see text]