measuring fatty acid oxidation in gliomas using 18f-fpia pet/mri

Conditions: Glioma

Summary: glioma is the most common primary malignant brain tumour in adults and has an extremely poor prognosis. the aim of this study is to quantify the degree of early step fatty acid oxidation in gliomas as imaged by 18f-fpia pet/mri in 10 evaluable patients. the investigators hypothesise that fpia uptake will be higher in high-grade gliomas compared to lower grade gliomas, in keeping with a higher propensity of high grade tumours to generate atp and nadph via fatty acid oxidation under bioenergetic stress.

10 evaluable participants with suspected cerebral glioma on previous mri who are due to undergo surgical resection or biopsy will be enrolled into the study. the patients invited to participate in the study will provide full consent, but will only undergo 18f-fpia pet/mri imaging once they have satisfied the inclusion and exclusion criteria. once these have been satisfied, eligible participants will proceed to 18f-fpia pet/mri. on the day of imaging the participants will undergo a blood test to measure plasma concentrations of carnitine. 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 participant will receive an additional iv bolus of gadolinium contrast medium administered through a peripheral venous cannula. arterial blood sampling through a peripheral arterial line will be performed to determine the concentration of radiotracer within arterial plasma. all the participants that are enrolled into the study will undergo biopsy or surgical resection as part of their routine clinical care, from which their tumour grade will be confirmed; the investigators will obtain tissue from these procedures to perform metabolomics, genomics and proteomics. surgery or biopsy will be performed typically within 2 weeks but no later than 3 months.

Eligibility criteria:
inclusion criteria: patients with radiological evidence of suspected cerebral glioma due for surgery or biopsy and with the following characteristics will be recruited: * age ≥18 * tumour size at least 2 cm. * who performance status 0 - 2. * 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 pregnancy test done at initial screening and on the day of tracer administration. the result of the pregnancy test must be known before administration of 18f-fpia injection. * the subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained. * the subject has a satisfactory medical history as judged by the investigator with no significant co-morbidities, physical examination, and vital signs findings during the screening period (from 21 days before administration). * the subject's clinical and laboratory tests are within normal limits and/or considered clinically insignificant. exclusion * the subject has received any chemotherapy, immunotherapy, biologic therapy or investigational therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of 18f-fpia injection. the subject is pregnant or lactating. * the subject is diabetic or has uncontrolled blood glucose or blood lipid levels (clinical decision by investigator), any other chronic illness that will preclude brief discontinuation of medication, or musculoskeletal condition that would not allow comfortable performance of a 66-minute study. * the subject has received another investigational radioactive tracer within 1 month before administration of 18f-fpia injection. * anticoagulation therapy, prolonged prothrombin time, abnormal allen's test. * unsatisfactory renal function (egfr\<60)

Keywords: pet/mri fatty acid oxidation