AB012. Tissue uptake of novel boron neutron capture therapy compounds in a mouse model, with pharmacokinetic and dosimetric extrapolation to human treatment
Abstract

AB012. Tissue uptake of novel boron neutron capture therapy compounds in a mouse model, with pharmacokinetic and dosimetric extrapolation to human treatment

Warren Kilby, Chad Lee, Michael Torgov, Tioga Martin, Linnette Capo, Maki Ikeura, Christina Malinao, Arthur Raitano, Karen Morrison, Kendall Morrison

TAE Life Sciences, Lake Forest, CA, USA

Correspondence to: Warren Kilby, MSc. TAE Life Sciences, 19631 Pauling, Foothill Ranch, Lake Forest, CA 92610, USA. Email: wkilby@taelifesciences.com.

Background: One promising candidate boron delivery compound for boron neutron capture therapy (BNCT) is a borylated tyrosine analog (BTS). Uptake of BTS is via the large amino transporter (LAT)-1, suggesting that BTS is applicable to similar indications as boronophenylalanine (BPA). BTS is more soluble and tumor-specific than BPA formulated in fructose (BPA-F) enabling higher tumor boron concentrations. In this study, the biodistribution of BTS after bolus injection in a small animal model is extrapolated to human treatment, and treatment plans are used to evaluate the potential clinical benefits of BTS vs. BPA-F.

Methods: BTS and BPA-F biodistributions were evaluated by inductively coupled plasma optical emission spectroscopy after bolus injection in a mouse xenograft model using a human nasopharyngeal cancer (FaDu). Compartment models were used to fit the biodistribution data. These were used to predict biodistribution in a human following infusion of 350 mg/kg BPA-F vs. 1,400 mg/kg BTS by allometric scaling for blood and brain, and fixed tissue:blood ratios for tumor and other tissues. Dose was calculated for an accelerator-generated epithermal neutron beam treatment of a large human nasopharyngeal cancer using Monte Carlo methods.

Results: BTS is more soluble than BPA, permitting 4× higher boron concentration in the same injection volume. At all times up to 10 hours post-injection, tumor and brain boron concentrations are >2.5× higher and >25% lower respectively with BTS in the mouse model. The treatment plan using BTS showed slightly lower normal tissue dose and significantly higher tumor dose than BPA-F [27.4 Gray-equivalent (Gy-Eq) tumor dose delivered to the median 50% of the tumor volume (D50%) vs. 10.7 Gy-Eq]. Alternatively, it is possible to normalize both plans to fixed tumor dose in which case the normal tissue doses and the treatment time are 2.6× lower for BTS than BPA-F.

Conclusions: Small animal experiments show significant tumor boron concentration enhancement and tumor specificity advantages for BTS vs. BPA-F. These can be extrapolated to humans using pharmacokinetic models. Radiation dose calculations show significant advantages for epithermal neutron beam BNCT using BTS vs. BPA-F in terms of tumor dose increase, normal tissue dose decrease, and treatment time reduction. The next step is small animal efficacy testing of BTS vs. BPA-F at the Kyoto University Research Reactor.

Keywords: Boron neutron capture therapy (BNCT); head and neck cancer; boron delivery compounds

Acknowledgments

The authors would like to thank their colleagues, particularly in the drug development and dose calculation service development teams, for their contributions to this work.

Footnote

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab012/coif). All authors are employees of TAE Life Sciences. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Ethical approval or informed consent is not required as there’s no human participants involved in this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/tro-25-ab012
Cite this abstract as: Kilby W, Lee C, Torgov M, Martin T, Capo L, Ikeura M, Malinao C, Raitano A, Morrison K, Morrison K. AB012. Tissue uptake of novel boron neutron capture therapy compounds in a mouse model, with pharmacokinetic and dosimetric extrapolation to human treatment. Ther Radiol Oncol 2025;9:AB012.

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