Hyperpolarised Carbon-13 MRI
Hyperpolarised carbon-13 MRI is an emerging technique for imaging.
Cambridge has two clinical hyperpolarisers for carbon-13 MRI studies currently being run at the Cambridge Biomedical Campus. 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 is exploring applications of this technique in cancer imaging as well as other applications such as multiple sclerosis and stroke and is/has been funded by Cancer Research UK, The Wellcome Trust, The Mark Foundation, Addenbrooke’s Charitable Trust, the CRUK Cambridge Centre, The MS Society, Prostate Cancer UK, and the Evelyn Trust. The metabolism of two molecules – pyruvate and fumarate – is being studied in a number of different cancer types.
Background
The design for the SPINLab Diamond Polariser, based on the dissolution-dynamic nuclear polarisation technique (DNP), was first presented in 2010 by GE (GE Research Circle Technology). The 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. The SPINLab is linked to an automated control subsystem for sample analysis, the “QC module”. Hyperpolarised 13C-pyruvate can be used to image metabolism in tissue by measuring the exchange or flux of the hyperpolarised 13C label in the pyruvate into other metabolites such as lactate and bicarbonate.
SPINLab Pharmacy Kits
The SPINLab Pharmacy Kit is designed to contain all the components required for hyperpolarisation, dissolution and subsequent QC processes within one 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 cabinet.
Clinical studies
At Cambridge we have a number of studies open and actively recruiting cancer patients with a variety of different cancer types, such as brain tumours, breast tumours, liver masses, ovarian masses, pancreatic masses, prostate tumours and renal masses and also patients with non-cancer diagnoses such as multiple sclerosis. We have the ability to image healthy volunteers to act as control subjects to compare against the disease patients.
The above mentioned studies are recruiting for pyruvate injection and we are currently setting up an ethically approved study for the injection of the molecule fumarate in a small number of cancer types.
The aim of these pilot studies are to determine whether hyperpolarised 13C-pyruvate or 13C‑fumarate can show altered physiology of cells compared to healthy cells.
Global Project Status
SPINLab Diamond Polariser and QC module
There are currently only a small number of sites worldwide with a SPINLab: together we are developing this technology to improve.
