Hyperpolarized Pyruvate Injection in Subjects With Prostate Cancer

This is a phase 1 clinical study of an investigational medicinal product (IMP), hyperpolarized Pyruvate (13C) Injection. The study includes the acquisition of magnetic resonance (MR) data and will be performed in men with prostate cancer and intact prostates. A standard dose-escalation design will be used; initially, 6 subjects will receive IMP at each dose level. As data on both the dynamics of arrival of the IMP and potential imaging efficacy are needed at each dose level, requiring the use of separate MR acquisition sequences, a modified 3+3 design will be applied in each dose cohort. The first 3 subjects will undergo dynamic 13C imaging to define the kinetics of delivery and metabolism of IMP, and the second 3 subjects will undergo 13C MR spectroscopic imaging (MRSI) to obtain 3-dimensional (3-D) spatial information about metabolism of IMP in regions of the prostate with and without cancer involvement. After the apparent maximum tolerated dose (MTD) has been established, there will be an expansion of the 3-D imaging cohort to 6 subjects (9 subjects in total at this dose level) to obtain additional information regarding safety at the MTD. If \>2 subjects from this cohort of 9 subjects experience a dose-limiting toxicity (DLT), the next lower dose will be defined as the MTD. At the dose level with the highest contrast to noise ratio (dose level less than or equal to the MTD) there will be an expansion of the imaging cohort to include another 15 subjects for a total of 18 subjects who undergo 13C 3-D scanning at this dose, to obtain exploratory information concerning the time course and SNR (signal to noise ratio) of the presence of hyperpolarized \[1 13C\] pyruvate and its metabolites in regions of cancer and benign prostate tissues. The information provided by these data will be used to develop the MR imaging protocol for future clinical trials that will seek to address the sensitivity and specificity of the technology.