Cerebral Metastases
Conditions
Keywords
PET/MRI, Fatty Acid Oxidation
Brief summary
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.
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.
Interventions
OTHER[18F]FPIA PET/MRI
18F-fluoropivalate tracer injection followed by PET/MRI scan
Sponsors
Imperial College London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients. | On the scan day up to 60 minutes | 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. |
| Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS). | On the scan day (4-8 weeks post-SRS treatment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | On the scan day (4-8 weeks post-SRS treatment) | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was open to recruitment from Intervention: Administration of \[18F\]FPIA followed by the performance of a positron emission tomography-multiparametric magnetic resonance imaging (PET-mMRI) performed at Invicro, Centre for Imaging Sciences, Burlington Danes, Imperial College London (Hammersmith Hospital Campus), Du Cane Road, London, W12 0NN. The aim of the study was to quantify the degree of early step fatty acid oxidation in cerebral metastases as imaged by \[18F\]FPIA PET-mMRI.
Participants by arm
| Arm | Count |
|---|---|
| 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 for their IMD at the time of enrolment/\[18F\]FPIA positron emission tomography-multiparametric magnetic resonance imaging (PET-mpMRI).
Participants enrolled into the study had an \[18F\]FPIA PET-mpMRI scan 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. | 12 |
| 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 positron emission tomography multiparametric magnetic resonance imaging (PET-mpMRI).
Participants enrolled into the study had an \[18F\]FPIA PET-mpMRI scans performed at the Invicro, Centre for Imaging Sciences. A single intravenous dose of \[18F\]FPIA (maximum, 370 MBq) was administered to the participant followed by a whole brain dynamic PET-MRI scan over 66 minutes. | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Patients With Radiological Evidence of IMD That Are Treatment Naive. | Patients With Radiological Evidence of IMD That Had Completed Stereotactic Radiosurgery. | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 4 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Continuous | 67.5 years | 62.5 years | 64 years |
| Extracranial tumour of origin Breast | 2 Participants | 3 Participants | 5 Participants |
| Extracranial tumour of origin Colorectal | 1 Participants | 0 Participants | 1 Participants |
| Extracranial tumour of origin Lung | 8 Participants | 6 Participants | 14 Participants |
| Extracranial tumour of origin Melanoma | 1 Participants | 1 Participants | 2 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 |
| other Total, other adverse events | 0 / 12 | 0 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
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.
Time frame: On the scan day (4-8 weeks post-SRS treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS). | T1 mask | 1.45 SUVmax (kBq/L/kBq/g) | Standard Deviation 0.65 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS). | SUV40 mask | 1.15 SUVmax (kBq/L/kBq/g) | Standard Deviation 0.56 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Patients Treated With Stereotactic Radiosurgery (SRS). | SUV30 mask | 1.17 SUVmax (kBq/L/kBq/g) | Standard Deviation 0.54 |
Primary
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.
Time frame: On the scan day up to 60 minutes
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients. | T1 mask | 1.54 SUV_max (kBq/L/kBq/g) | Standard Deviation 0.41 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients. | SUV40 mask | 1.47 SUV_max (kBq/L/kBq/g) | Standard Deviation 0.33 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Quantitative Measurement of [18F]FPIA Uptake Within the Cerebral Metastases of Treatment naïve Patients. | SUV30 mask | 1.48 SUV_max (kBq/L/kBq/g) | Standard Deviation 0.33 |
Secondary
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.
Time frame: On the scan day (4-8 weeks post-SRS treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | T1 mask | 3.75 TBRmax | Standard Deviation 1.16 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | SUV40 mask | 3.71 TBRmax | Standard Deviation 1.21 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With Treatment-naive IMD on CE-MRI. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | SUV30 mask | 3.73 TBRmax | Standard Deviation 1.19 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With IMD on CE-MRI That Had Undergone SRS Treatment. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | T1 mask | 3.97 TBRmax | Standard Deviation 1.82 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With IMD on CE-MRI That Had Undergone SRS Treatment. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | SUV40 mask | 3.85 TBRmax | Standard Deviation 1.99 |
| [18F]FPIA PET-mMRI Scans Performed on Patients With IMD on CE-MRI That Had Undergone SRS Treatment. | Distribution of [18F]FPIA Uptake in Lesions Which Have Undergone Treatment, With Those That Are Treatment naïve. | SUV30 mask | 3.90 TBRmax | Standard Deviation 1.94 |