Quantification of Boron Compound Concentration for BNCT Using Positron Emission Tomography

Abstract

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 SUVmax). 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-BFn, where 1 <= n <= 3, labeled with 18F relatively easily, as in our example. A patient may undergo injection of a mixture of nonradioactive R-BFn to reach the necessary 10B concentration for BNCT treatment in the tumor together, with [18F]R-BFn for boron mapping.

Clinical Viability of Boron Neutron Capture Therapy for Personalized Radiation Treatment

“…In the paper [ 86 ], Balcerzyk et al explored the possibility of PET measurement of boron concentration if the compound contains the R -BF 3 moiety that labels it with 18 F. This method was applied to [ 18 F]NaBF4 used in the preclinical study of thyroid cancer.…”

Research facilities and highlights at the Centro Nacional de Aceleradores (CNA)

“…Since 2012, 14 C Accelerator Mass Spectrometry measurements are performed in a dedicated system at CNA (Fig. 4).…”

“…The application of these 6 infrastructures covers fields as diverse as material sciences, environmental impact, nuclear and particle physics, nuclear instrumentation, medical imaga e-mail: gomez@us.es (corresponding author) 0123456789(). : V,-vol ing, biomedical research and preclinical molecular imaging, 14 C dating and irradiation in samples of technological and biological interest, among others.…”

Physical bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action - Critical Overview of the Literature

“…In the paper [73], Balcerzyk et al explored the possibility of PET measurement of boron concentration if the compound contains R-BF3 moiety labeling it with 18 F. This method was applied to [ 18 F]NaBF4 used in thyroid cancer preclinical study.…”