Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography

Background: Boron neutron capture therapy requires a 2 mM ¹⁰B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [¹⁸F]fluoroBPA ([^18F]FBPA) as an agent to qualify for treatment. Precisely, [¹⁸F]FBPA must have at least a 3:1 tumor to background tissue ratio to qualify the patient for BNCT treatment. Normal, hyperplasia, and cancer thyroids capture iodine and several other large ions, including BF₄^-, through a sodium-iodine symporter (NIS) expressed on the cell surface in normal conditions. In cancer, NIS is also expressed within the thyroid cell and is not functional. Methods: To visualize the thyroids and NIS, we have used a [¹⁸F]NaBF₄ positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [¹⁸F]NaBF₄ PET tracer was produced from NaBF₄ by the isotopic exchange of natural ¹⁹F with radioactive ¹⁸F. Rats were subject to hyperplasia and tumor-inducing treatment. The NIS in thyroids was visualized by immunofluorescence staining. The boron concentration was calculated from Standard Uptake Values (SUV) in the PET/CT images and from the production data. Results: 41 MBq, 0.64 pmol of [¹⁸F]NaBF₄ PET tracer that contained 0.351 mM, 53 nmol of NaBF₄ was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUV_max). The ^natB concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [¹⁰B]NaBF₄ to reach the necessary 2 mM ¹⁰B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the ¹³¹I used now, there is no post-treatment radioactive decay, the patient can be immediately discharged from hospital, and there is no six-month moratorium for pregnancy. This method can be used for BNCT treatment compounds of the type R-BF_n, where 1 <= n <= 3, labeled with ¹⁸F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BF_n to reach the necessary ¹⁰B concentration for BNCT treatment in the tumor together, with [¹⁸F]R-BF_n for boron mapping.