Measuring Fatty Acid Oxidation in Cerebral Metastases Using [18F]FPIA

Determining the Magnitude of Early Steps of Fatty Acid Oxidation in Cerebral Metastases Using [18F]FPIA PET/MRI

Cerebral metastases represent a significant problem for oncological management. It is estimated that 20-40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness. 18F-fluoropivalate ([18F]FPIA) is a new tracer that images short chain fatty acid (SCFA) uptake in tumours, a key component of fatty acid oxidation.

The aim of this study is to quantify the degree of early step fatty acid oxidation in cerebral metastases as imaged by [18F]FPIA Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI).

The investigators hypothesise that FPIA uptake will be higher in metastases that are treatment naïve compared to those that have undergone treatment, in keeping with viable tumour cells having a high propensity to generate ATP and NADPH via fatty acid oxidation under bioenergetic stress.

Study Overview

• Status: Completed
• Conditions: Cerebral Metastases
• Intervention / Treatment: Other: [18F]FPIA PET/MRI

Detailed Description

24 evaluable patients with radiological evidence of cerebral metastases on MRI will be enrolled into the study (12 who are treatment naïve + 12 who have completed Stereotactic Radiosurgery (SRS)+/- combination therapy). The patients invited to participate in the study will provide written informed consent. [18F]FPIA PET/MRI imaging will only be performed once patients have satisfied the inclusion and exclusion criteria. Once these have been satisfied, eligible patients will proceed to [18F]FPIA PET/MRI.

On the day of imaging the patients will undergo a blood test to measure plasma concentrations of carnitine (approximately 6mls). During the scan, a single dose of [18F]FPIA (maximum, 370 MBq) IV will be administered to the participant followed by a whole brain dynamic PET/MRI scan over 66 minutes. During the MRI sequences, the patient will receive a 2 stage IV bolus of Gadolinium contrast medium administered through a peripheral venous cannula.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with radiological evidence of cerebral metastases on MRI that are either treatment naïve or have been treated with SRS +/- combination therapy within 4-8 weeks.

Description

Inclusion Criteria:

A) Treatment naïve

or

B) SRS+/- combination treated - Patients that have completed the SRS part of a combination regime enabling a 4-8 week post-SRS treatment PET/MRI scan.

and

C) That fulfil the following criteria:

1. Age ≥18.
2. Target metastases size ≥ 1cm.
3. WHO performance status 0 - 2.
4. If female, the subject is either post-menopausal (at least 1 year), or surgically sterilized (has had a documented bilateral oophorectomy and/or documented hysterectomy for at least 2 years), or if of childbearing potential, must have a negative urine beta human chorionic gonadotropin (beta-hCG) pregnancy test done prior to tracer administration.
5. The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
6. The subject has a satisfactory medical history as judged by the investigator with no significant co-morbidities.
7. The subject's clinical and laboratory tests are within normal limits and/or considered clinically insignificant.

Exclusion Criteria:

1. The subject is pregnant or lactating.
2. Any other chronic illness that will or musculoskeletal condition that would not allow comfortable performance of a PET study.
3. Prior use within 14 days of enrolment or concurrent therapy with any other investigational agent.
4. Unsatisfactory renal function (eGFR<30).
5. The subject has non-MRI compatible devices (e.g.a pacemaker, an implantable cardioverter-defibrillator (ICD), a nerve stimulator, a cochlear implant or a drug pump) or implanted material (e.g. non-MRI compatible sternal wires, biostimulators, metals or alloys).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients With Radiological Evidence of IMD That Are Treatment Naive.; Participants with radiological evidence of intracranial metastatic disease (IMD) on standard of care contrast-enhanced magnetic resonance imaging (CE-MRI) that were treatment-naive at the time of enrolment/[18F]FPIA PET-mpMRI scanning. Participants enrolled into the study had [18F]FPIA positron emission tomography-multiparametric magnetic resonance imaging (PET-mMRI) scan(s) performed at the Invicro, Centre for Imaging Sciences. A single intravenous dose of [18F]FPIA (maximum, 370MBq) was administered to the participant followed by a whole brain dynamic PET-MRI scan over 66 minutes.	Other: [18F]FPIA PET/MRI; 18F-fluoropivalate tracer injection followed by PET/MRI scan; Other Names: Imaging Scan
Patients With Radiological Evidence of IMD That Had Completed Stereotactic Radiosurgery.; Participants with radiological evidence of intracranial metastatic disease (IMD) on standard of care contrast-enhanced magnetic resonance imaging (CE-MRI) that had completed stereotactic radiosurgery (SRS) (+/- combination therapy) within 4-8 weeks of [18F]FPIA PET-mMRI. Participants enrolled into the study had [18F]FPIA positron emission tomography-multiparametric magnetic resonance imaging (PET-mMRI) scans performed at the Invicro, Centre for Imaging Sciences. A single intravenous dose of [18F]FPIA (maximum, 370MBq) was administered to the participant followed by a whole brain dynamic PET-MRI scan over 66 minutes.	Other: [18F]FPIA PET/MRI; 18F-fluoropivalate tracer injection followed by PET/MRI scan; Other Names: Imaging Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients.	Standardised uptake value (SUV) at 60 minutes post-injection of [18F]FPIA assessed using PET/MRI. SUV is a semiquantitative measurement of radiotracer uptake in tissue. It is a ratio of tissue radioactivity concentration at a point in time within a specific region of interest and the injected dose of radioactivity per kilogram of the patient's body weight. SUVmax is the highest SUV value within a region of interest.	On the scan day up to 60 minutes
Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS).	Standardised uptake value (SUV) at 60 minutes post-injection of [18F]FPIA assessed using PET/MRI. SUV is a semiquantitative measurement of radiotracer uptake in tissue. It is a ratio of tissue radioactivity concentration at a point in time within a specific region of interest and the injected dose of radioactivity per kilogram of the patient's body weight. SUVmax is the highest SUV value within a region of interest.	On the scan day (4-8 weeks post-SRS treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve.	Tumour-to-contralateral white matter (CWM) ratio (TBR) 60 minutes post-injection of [18F]FPIA using PET/MRI. Regions of interest for quantification were identified by an experienced neuroradiologist. For each subject, two volumes of interest (VOI) were created. A VOI was drawn around the lesion, plus a contralateral VOI of the same volume in healthy brain was measured for comparison using a T1-MRI mask, SUV30 mask and SUV40 mask. The maximum standardised uptake value (SUVmax) of [18F]FPIA within the tissues was calculated using the last PET frame at 60 minutes. SUV30 and SUV40 masks (30 and 40% of the SUVmax value at 60 minutes) were derived to determine image overlap.	On the scan day (4-8 weeks post-SRS treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of [18F]FPIA variables with volumetric and functional MRI variables including perfusion.	PET/MRI	At study completion, average of 1 year.

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: PET/MRI; Fatty Acid Oxidation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 19CX5551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No