Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography
2020
Marcin Balcerzyk | Manuel De-Miguel | Carlos Guerrero | Begoña Fernandez
Background: Boron neutron capture therapy requires a 2 mM <sup>10</sup>B concentration in the tumor. The well-known BNCT patient treatment method using boronophenylalanine (BPA) as a boron-carrying agent utilizes [<sup>18</sup>F]fluoroBPA ([<sup>18F</sup>]FBPA) as an agent to qualify for treatment. Precisely, [<sup>18</sup>F]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 BF<sub>4</sub><sup>−</sup>, 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 [<sup>18</sup>F]NaBF<sub>4</sub> positron emission tomography (PET) tracer. It was injected into the tail veins of rats. The [<sup>18</sup>F]NaBF<sub>4</sub> PET tracer was produced from NaBF<sub>4</sub> by the isotopic exchange of natural <sup>19</sup>F with radioactive <sup>18</sup>F. 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 [<sup>18</sup>F]NaBF<sub>4</sub> PET tracer that contained 0.351 mM, 53 nmol of NaBF<sub>4</sub> was injected into the tail vein. After 17 min, the peak activity in the thyroid reached 2.3 MBq/mL (9 SUV<sub>max</sub>). The <sup>nat</sup>B concentration in the thyroid with hyperplasia reached 381 nM. Conclusions: Such an incorporation would require an additional 110 mg/kg dose of [<sup>10</sup>B]NaBF<sub>4</sub> to reach the necessary 2 mM <sup>10</sup>B concentration in the tumor. For future BNCT treatments of thyroid cancer, contrary to the <sup>131</sup>I 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<sub>n</sub>, where 1 <= n <= 3, labeled with <sup>18</sup>F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BF<sub>n</sub> to reach the necessary <sup>10</sup>B concentration for BNCT treatment in the tumor together, with [<sup>18</sup>F]R-BF<sub>n</sub> for boron mapping.
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