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

Purpose 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-[¹⁸F]fluoro-L-phenylalanine ([¹⁸F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible. Methods We studied dynamic uptake of [¹⁸F]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. [¹⁸F]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 [¹⁸F]FBPA tissue activity gradients. Results Model fits with three parameters K ₁ (transport), k ₂ (reverse transport) and k ₃ (intracellular metabolism) were found to best illustrate [¹⁸F]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 [¹⁸F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [¹⁸F]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. Conclusion [¹⁸F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [¹⁸F]FBPA, some of these benign neoplasms may be amenable to BNCT. Financial support: This work was sponsored in part by the Department of Army, Grant No. DAMD17-00-1-0545. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014, USA, is the awarding and administering acquisition office. The content of the information of this paper does not necessarily reflect the position or the policy of the US Government.