Hyperpolarised Carbon-13: Cancer Imaging
Cambridge has installed one of the world’s first clinical hyperpolarisers for carbon-13 MRI. Hyperpolarisation increases the signal-to-noise of carbon-13 on MRI by 10,000-100,000 fold and allows metabolism of 13C containing molecules to be detected and imaged in real-time. The project will explore applications of this technique in cancer imaging and has been funded by the Wellcome Trust, Cancer Research UK, Addenbrooke’s Charitable Trust, the Cambridge Cancer Centre and Prostate Cancer UK. The metabolism of two molecules – pyruvate and fumarate – will be studied in glioma, lymphoma and breast and ovarian cancer.
The design for the SPINlab Diamond Polariser, based on the dissolution-dynamic nuclear polarisation technique (DNP)1, was first presented in 2010 by GE (GE Research Circle Technology, Inc.)2. SPINlab hyperpolarises MR-sensitive nuclei, such as 13C, increasing the MR signal by 10,000 to 100,000 fold. The conditions required for polarisation include high magnetic field (5 Tesla), a very low temperature (~1K), a radical or electroparamagnetic additive (EPA), and microwave irradiation. SPINlab can be linked to an automated control subsystem for sample analysis, the “QC module”. The current QC module is optimised for use with 13C-pyruvate. Hyperpolarised 13C-pyruvate can be used to image metabolic rates in tissue by measuring the flux of the hyperpolarised 13C label from the pyruvate into other metabolites.
Sterile fluid path
The sterile fluid path is designed to contain all the components required for hyperpolarisation, dissolution and subsequent QC processes within one sterile disposable unit. It consists of a sample vial, dual-tube lumen with valves and seals, syringes for water and buffer, and a receiver unit with filter to receive the final sample for injection.
The sample vial can be filled with the 13C/EPA mixture (DPmix) and sealed to the outer tubing with a single radial laser weld. The filling of the fluid path needs to be performed in a sterile environment, e.g. a Grade A laminar flow hood.
The first clinical protocol for a series of single-centre studies in Cambridge with hyperpolarised 13C-pyruvate has been developed. This first study is an MR pilot in healthy volunteers and patients with liver metastases.
The aim of the pilot study is to determine whether hyperpolarised 13C-pyruvate can show altered physiology of cancer cells compared to healthy cells. Additional studies are planned in glioma, lymphoma, ovarian, breast and prostate cancer, as well as in other fields.
Global Project Status
SPINLab Diamond Polariser and QC module
There are currently thirteen sites worldwide with a SPINlab, of which six are in Europe. The majority of the sites also have the QC module installed.
Sterile fluid paths
The SPINLab site in San Francisco is set-up as a Production facility to fill sterile fluid paths, as is Memorial Sloan Kettering Cancer Center. Cambridge will be the third Production site.
The University of California San Francisco published the first-in-man study with hyperpolarised 13C-pyruvate in prostate cancer3. Planned future SPINLab studies include imaging in Oncology, Neurology and Cardiovascular disease.
Kevin Brindle (CRUK Cambridge Institute)
Bristi Basu (Oncology)
Anita Chhabra (Pharmacy)
Arnaud Comment (GE Healthcare)
Vicky Fernandes (Pharmacy)
Martin Graves (MR Physics)
Mary McLean (CRUK Cambridge Institute)
Kishor Solanki (Radiopharmacy)
Ian Wilkinson (Medicine)