Hyperpolarized Carbon-13 Imaging of Metastatic Prostate Cancer

A pilot study with a group of up to 10 men with CRPC about to embark on a 6-month course of treatment with radium 223. Study participants will undergo anatomical MR imaging combined with the new hyperpolarized MRI (1 hour exam) prior to treatment.

"Hyperpolarization" of low natural abundance species such as 13C, offers the potential of extracting metabolic information by real-time imaging of biochemical reactions within the body. In this project, the investigators focus on prostate cancer, specifically late-stage disease, as management of these patients would benefit from a new imaging method that enables improved therapy selection, planning and monitoring. For imaging the lactate distribution in bone-metastatic prostate cancer, 3D coverage of a large field-of-view is required in order to cover the vertebral column (the most common site of metastases). To enable this, the investigators have developed methods using a large-volume transmitter and multi-channel receiver system for 3-dimensional 13C metabolic imaging in these patients. The image resolution and encoding matrix were tailored to the required 3D coverage of the vertebral column. At the end of this study, the investigators will have the methodology, hardware and clinical-research workflow needed to evaluate 13C-lactate imaging as a new tool to help patients with metastatic prostate cancer. The investigators would be the first in the world to apply 13C metabolic MRI to bone metastases. Although the investigators propose to study patients who are starting a 6-month course of treatment with radium 223, in this project, this proof-of-concept study may also lead to a larger clinical trial at different points in the treatment pathway, such as prior to deciding between treatment with cytotoxic agents versus drugs that target the androgen axis such as abiraterone.

"Hyperpolarization" of low natural abundance species such as 13C, when injected offers the potential of extracting metabolic information by real-time MR imaging of biochemical reactions within the body. The biochemical reactions, including lactate production, will be measured using MRI.

Inclusion Criteria: Men with bone-metastatic CRPC before starting the first dose of radium 223 therapy Laboratory requirements: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x109/L Hemoglobin ≥ 10.0 g/dL (100 g/L; 6.2 mmol/L) Total bilirubin level ≤ 1.5 institutional upper limit of normal (ULN) ASAT and ALAT ≤ 2.5 ULN • Creatinine ≤ 1.5 ULN Albumin >25 g/L Eastern Cooperative Oncology Group Status of 0 or 1 Exclusion Criteria: Unable to give valid informed consent Contraindication for MRI as per Sunnybrook MRI questionnaire (Appendix 1). Claustrophobia Body mass index of less than 18.5 or greater than 32 Congestive heart failure, a past or present medical history of clinically significant electrocardiogram (EKG) abnormalities, which may include QT prolongation, a family history of prolonged QT interval syndrome, or a myocardial infarction (MI) within the past 12 months with ensuing unstable EKG, or ongoing acute or chronic pulmonary bronchospastic disease, including a history of chronic obstructive pulmonary disease or asthma, with an exacerbation within the past year