This is a pilot clinical study of hyperpolarized pyruvate (13C) injection that includes the
acquisition of magnetic resonance (MR) data and will be performed in men with localized
prostate cancer. Part 1: Five patients will be evaluated for reproducibility of 13C HP MR
imaging measurements obtained 2-3 weeks apart with no interim treatment. Part 2: Five
patients will be evaluated for the change in 13C HP MR imaging measurements after 2 months
13C HP MR data will be acquired in two parts of the study (which can occur simultaneously):
Part 1: Patients will undergo imaging at baseline and will be repeated two to three weeks
later (with no intervention in the interim) to evaluate reproducibility.
Part 2: Patients will undergo imaging at baseline, initiate androgen deprivation therapy,
and undergo repeat imaging two months after initiation of ADT to evaluate the ability of the
imaging to reflect a metabolic response to treatment.
The change in pyruvate/lactate ratio and lactate levels will be measured and compared to
baseline at these timepoints.
- The subject has biopsy-proven adenocarcinoma of the prostate with intermediate to
high risk disease by UCSF CAPRA scoring and possesses a Gleason 4 component to the
tumor. Subjects will be enrolled either prior to radical prostatectomy (N=5) or prior
to 2 months of androgen deprivation therapy (LHRH agonist +/- antiandrogen) followed
by definitive radiation therapy as their primary treatment for prostate cancer (N=5).
- The subject is able and willing to comply with study procedures and provide signed
and dated informed consent.
- At least 5 mm of tumor on biopsy (can have multiple cores to comprise 5 mm).
- The subject has concordant MRI/1H MRSI findings from a MR staging exam at UCSF
performed prior to the 13C MRSI exam performed in this study with IMP, or is willing
to undergo MRI/1H MRSI in connection with the study exam.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Laboratory criteria for protocol entry:
- Absolute neutrophil count (ANC) ≥1000 cells/µL
- Hemoglobin ≥9.0 gm/dL
- Platelets ≥75,000 cells/µL
- Estimated creatinine clearance ≥50 mL/min
- Total bilirubin ≤1.5x ULN (or if ≤4 gm/dL and direct bilirubin is WNL)
- Aspartate aminotransferase (AST) ≤1.5x ULN
- Alanine aminotransferase (ALT) ≤1.5x ULN
- Willing to use contraception during and for 1 month after completion of the study.
- For part 2 of the study: plans to initiate castrating therapy (with a GnRH
antagonist, GnRH agonist, or orchiectomy). An antiandrogen may be started after
initial imaging but can not be used prior to baseline imaging. An antiandrogen is
allowed but not required.
- The subject has received, or is scheduled to receive, another IMP from 1 month before
to 1 month after inclusion in this study.
- Current or prior androgen deprivation therapy; previous use of a 5-α reductase
inhibitor is allowed, provided it was discontinued at least one month prior to study
- Poorly controlled hypertension, with blood pressure at study entry>160/100.
- Contraindication for or inability to tolerate MRI examination.
- Prostate biopsy within 12 weeks prior to study entry.
- BMI of less than 18.5 or greater than 32. Subject body weight should be less than or
equal to 100 kg owing to limitations in the amount of IMP available.
- Congestive heart failure or New York Heart Association (NYHA) status≥2.
- A history of clinically significant EKG abnormalities, including QT prolongation, a
family history of prolonged QT interval syndrome, or myocardial infarction (MI) less
than 1 year ago with ensuing unstable EKG.
- Ongoing acute or chronic pulmonary bronchospastic disease, including a history of
chronic obstructive pulmonary disease or asthma, with an exacerbation within the past