Measuring Fatty acid oxidation in cerebral metastases using 18F-FPIA

  • Research type

    Research Study

  • Full title

    Determining the magnitude of early steps of fatty acid oxidation in cerebral metastases using 18F-FPIA PET/MRI

  • IRAS ID

    272728

  • Contact name

    Matthew Williams

  • Contact email

    matt.williams3@nhs.net

  • Sponsor organisation

    Imperial College London

  • Clinicaltrials.gov Identifier

    N/A, N/A

  • Duration of Study in the UK

    4 years, 0 months, 0 days

  • Research summary

    Tumours have increased energy demands to allow for their rapid growth compared to healthy cells. Glucose is the main source of energy in the healthy brain, however it has been shown that brain tumour cells can create energy in a different way which involving fatty acid metabolism. We believe that we can measure how much of this process is going on based on the amount of tracer and contrast the brain tumour cells take in during the PET/MRI scan.

    We will look at 24 patients who already have radiological evidence of brain metastases on standard MRI imaging; 12 patients who have not had treatment and 12 patients who have undergone stereotactic radiosurgery. Each patient will have one PET/MRI scan using the 18F-FPIA tracer and Gadolinium contrast lasting approximately 66 minutes.

    This will provide the opportunity to investigate the degree of fatty acid oxidation between untreated and treated patient groups, as well as differences in fatty acid metabolism between brain metastases from different primary tumours.
    We think that by comparing the scans of both groups with each other, we will see a difference in the amount of fatty acid metabolism between them.

    Participants will also have a blood test for carnitine levels (a natural substance in the body which plays a vital role in fatty acid metabolism/energy production). We will look for a relationship between blood levels of carnitine and the scan findings.

    We hope that the information from this study can help us understand how and why brain tumours grow, and provide us with important information, helping us to develop new treatments and medical tests in the future.

    The study will not involve any change to the patients normal clinical pathway.

    Lay summary of study results
    The incidence of brain metastases is increasing, in part due to the advances that have been made in systemic therapies to control disease outside of the brain. Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the standard of care (SoC) imaging for brain metastases. However, there are limitations to this imaging approach including limited prognostic information. This study investigates a new diagnostic approach of hybrid Positron Emission Tomography-multiparametric MRI (PET-mMRI) using a novel radiotracer [18F]fluoropivalate ([18F]FPIA). Twelve PET-mMRI scans were performed in patients with a diagnosis of brain metastases on SoC imaging that had not undergone any treatment for their brain metastases. A further 10 PET-mMRI scans were performed in patients that had been treated with stereotactic radiosurgery (SRS) within 4-8 weeks. One participant (P015) had two PET-mMRI scans as part of the study – one prior to SRS and one 4-8 weeks post-SRS. High radiotracer ([18F]FPIA) uptake was seen in all brain metastases compared to healthy brain tissue, regardless of where the primary tumour was in the body. This highlights the importance of [18F]FPIA PET-mMRI in both the detection of brain metastases and in follow-up surveillance, which is a challenge for CE-MRI. Tumour volumes measured using [18F]FPIA PET-mMRI were larger (~40%) than that measured using CE-MRI in the treatment-naïve tumours. This trend was reversed in the post-SRS cohort, with PET-mMRI volumes smaller than those measured on CE-MRI. One possible explanation for this, is the detection of pseudoprogression in patients treated with SRS that was not detected by PET-mMRI. Pseudoprogression is a treatment-related increase in tumour size on imaging that is subsequently followed by tumour shrinkage. The patients with tumours exhibiting the greatest level of [18F]FPIA radiotracer uptake (SUVmax ≥ 2.0) showed particularly short overall survival (median 4 v. 15 months). PET-mMRI therefore provides a non-invasive prediction of overall-survival, whereas the CE-MRI was uninformative. In summary, [18F]FPIA PET-mMRI offers a relevant approach to detect brain metastases in both treatment naïve patients and those on follow-up surveillance, whilst also providing important prognostic information.

    Lay summary of study results: The incidence of brain metastases is increasing, in part due to the advances that have been made in systemic therapies to control disease outside of the brain. Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the standard of care (SoC) imaging for brain metastases. However, there are limitations to this imaging approach including limited prognostic information. This study investigates a new diagnostic approach of hybrid Positron Emission Tomography-multiparametric MRI (PET-mMRI) using a novel radiotracer [18F]fluoropivalate ([18F]FPIA). Twelve PET-mMRI scans were performed in patients with a diagnosis of brain metastases on SoC imaging that had not undergone any treatment for their brain metastases. A further 10 PET-mMRI scans were performed in patients that had been treated with stereotactic radiosurgery (SRS) within 4-8 weeks. One participant (P015) had two PET-mMRI scans as part of the study – one prior to SRS and one 4-8 weeks post-SRS. High radiotracer ([18F]FPIA) uptake was seen in all brain metastases compared to healthy brain tissue, regardless of where the primary tumour was in the body. This highlights the importance of [18F]FPIA PET-mMRI in both the detection of brain metastases and in follow-up surveillance, which is a challenge for CE-MRI. Tumour volumes measured using [18F]FPIA PET-mMRI were larger (~40%) than that measured using CE-MRI in the treatment-naïve tumours. This trend was reversed in the post-SRS cohort, with PET-mMRI volumes smaller than those measured on CE-MRI. One possible explanation for this, is the detection of pseudoprogression in patients treated with SRS that was not detected by PET-mMRI. Pseudoprogression is a treatment-related increase in tumour size on imaging that is subsequently followed by tumour shrinkage. The patients with tumours exhibiting the greatest level of [18F]FPIA radiotracer uptake (SUVmax ≥ 2.0) showed particularly short overall survival (median 4 v. 15 months). PET-mMRI therefore provides a non-invasive prediction of overall-survival, whereas the CE-MRI was uninformative. In summary, [18F]FPIA PET-mMRI offers a relevant approach to detect brain metastases in both treatment naïve patients and those on follow-up surveillance, whilst also providing important prognostic information.

  • REC name

    South Central - Berkshire Research Ethics Committee

  • REC reference

    20/SC/0134

  • Date of REC Opinion

    23 Mar 2020

  • REC opinion

    Favourable Opinion