The scan can tell clinicians when a gene, responsible for activating a chemotherapy drug, is being expressed in cancer cells. The findings give a non-invasive way to measure the activity of gene therapy, which could lead to better, less toxic cancer treatments.
The research was published in the journal Molecular Imaging and Biologyand was funded by the (ICR) CR-UK & EPSRC Cancer Imaging Centre, with additional funding from The Wellcome Trust.
Conventional chemotherapy often has significant side effects, so researchers have pioneered a new approach where an inactive chemotherapy drug is given to patients.
In the new therapy, known as Gene Directed Prodrug therapy (GDEPT), a virus modified to carry the gene for an enzyme called CPG2 selectively infects cancer cells to produce CPG2, which then activates the chemotherapy drug. Neighbouring healthy cells are not affected by the inactive chemotherapy drug as they do not express the activating enzyme.
A critical step in the process is ensuring enough of the enzyme is being expressed in the cells to activate the drug. This new research shows a new type of MRI can identify when cells are producing enough enzyme, something that is likely to greatly improve the chance of success of this type of therapy.
The study used a new type of MRI to detect the release of glutamate - the hallmark by-product of the CPG2 enzyme - with very high sensitivity in real time.
Traditional MRI cannot detect glutamate directly but a technique called chemical exchange saturation transfer (CEST) MRI – which exploits the movement of protons between compounds like glutamate and water, the primary source of MRI – can sensitise MRI to glutamate.
When the researchers exposed a compound which mimics the non-toxic chemotherapy drug to the enzyme CPG2, the MRI recorded a signal as the compound was broken down to form glutamate.
The researchers then added the compound to CPG2-expressing colon carcinoma cells. They saw that the strength of the CEST MRI signal increased with time in proportion to the levels of glutamate released by CPG2 as it broke down the compound.
Study leader Dr Yann Jamin, post-doctoral training fellow in the Division of Radiotherapy and Imaging at The Institute of Cancer Research, said: “Cancer gene therapy holds a lot of promise; it should mean that we can target chemotherapy more effectively to tumours. Healthy tissues are unaffected so patients should be spared many of the side effects.
“We expect gene therapy using the CPG2 enzyme to go into trials soon. Our new MRI method means we will know the best time to give patients the inactivate drug, hopefully maximising the chance of this treatment succeeding.”