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An investigation of short-chain fatty acid uptake in solid tumours by [ 18F] fluoropivalate (FPIA) positron emission tomography and its relationship with tumour proliferation’ in glioma and other cancers

The role of fatty acid metabolism in tumour initiation, progression and therapeutic resistance is gaining attention. A novel radiotracer [ 18F]FPIA, is being developed by Professor Eric Aboagye’s group, for imaging the transcellular flux of short chain fatty acids (SCFAs) into tumour cells non-invasively by PET. An initial first in man study has shown favourable biodistribution (Figure) with primary renal excretion and low background activity in all organs aside from liver ( Dubash et al. 2020 EJNMMI). We are currently investigating the uptake of [ 18F]FPIA in a cohort of low-grade and high-grade gliomas, and the effect of chemo-radiotherapy on [ 18F]FPIA uptake/signal in glioma. An additional study is being planned for cerebral metastases.

A potential future use of [ 18F]FPIA is the imaging response to therapy, a process that is often associated with a change in proliferation or survival. We wish to determine whether the uptake of [ 18F]FPIA is proliferation-dependent or whether [ 18F]FPIA-PET is a proliferation-independent phenotype, which will establish the basis for data interpretation in future studies of [ 18F]FPIA PET.

The NCITA Exemplar 1 is a multicentre feasibility study which will assess the association between [ 18F]FPIA PET derived SCFA uptake in solid tumours and tumour proliferation. Patients will be scanned at NCITA host institutions, with patients scanned twice at the same institution to assess repeatability of [ 18F]FPIA PET imaging.

This study, in combination with on-going brain studies at Imperial College, will provide the data required to proceed to apply for further funding to perform a large powered multicentre study to evaluate treatment outcomes using [ 18F]FPIA PET imaging.

Figure: [18F]FPIA maximum intensity projection (MIP) image showing normal biodistribution in a healthy volunteer. Note minimal background activity aside from liver.