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

Autor: Payal Dixit, Shanu Modi, Mohammad Nasir Uddin, John F. Gerecitano, Mei Hsuan Chen, Tony Taldone, Jason S. Lewis, Komal Jhaveri, Brian Krichevsky, Mary L. Alpaugh, Devika Gajria, Gabriela Chiosis, Naga Vara Kishore Pillarsetty, Mark Dunphy, Erica Gomes DaGama, Steven M. Larson
Rok vydání: 2013
Předmět:
Zdroj: Journal of Clinical Oncology. 31:11076-11076
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2013.31.15_suppl.11076
Popis: 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]
Databáze: OpenAIRE
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