Uptake of 4-borono-2-[18F]fluoro-L-phenylalanine in sporadic and neurofibromatosis 2-related schwannoma and meningioma studied with PET

Meningiomas and schwannomas associated with neurofibromatosis 2 (NF2) are difficult to control by microsurgery and stereotactic radiotherapy alone. Boron neutron capture therapy (BNCT) is a chemically targeted form of radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET with the boron carrier 4-borono-2-[(18)F]fluoro-L-phenylalanine ([(18)F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible. We studied dynamic uptake of [(18)F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five sporadic and five NF2 patients. Tracer input function and cerebral blood volume were measured. [(18)F]FBPA uptake in tumour and brain was assessed with a three-compartmental model and graphical analysis. These, together with standardised uptake values (SUVs), were used to define tumour-to-brain [(18)F]FBPA tissue activity gradients. Model fits with three parameters K (1) (transport), k (2) (reverse transport) and k (3) (intracellular metabolism) were found to best illustrate [(18)F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher in tumour as compared with normal brain and independent of NF2 status. The increased uptake was due to higher transport of [(18)F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [(18)F]FBPA influx constant (K (i) -MTGA) ratios varied between 1.8 and 5.4 in NF2-associated tumours while in sporadic tumours the ratio was 1-1.4. [(18)F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [(18)F]FBPA, some of these benign neoplasms may be amenable to BNCT.