# Simulation-Based X-Ray Spectrum Optimization for Dose Enhancement in X-Ray-Induced Photodynamic Therapy with NaLuF4:20% Gd, 15% Tb3+ Nanocrystals

## TL;DR

This study identifies the optimal X-ray energy for enhancing X-ray-induced photodynamic therapy using nanocrystals, showing that 60 kVp provides the best therapeutic effect.

## Contribution

A Geant4-based simulation method is proposed to optimize X-ray energy for X-PDT, validated by correlating simulated doses with tumor growth inhibition.

## Key findings

- The 60 kVp X-ray beam produced the highest peak dose and maximum dose enhancement ratio.
- Simulated doses with nanoprobes correlated strongly with in vivo tumor growth inhibition rates.
- Absorbed dose peaks at shallow depths (<1.0 mm) in the tumor phantom.

## Abstract

Context: X-ray-induced photodynamic therapy (X-PDT) is an emerging modality for deep-tumor treatment, leveraging radiosensitizing nanoprobes to enhance therapeutic effects. Problem: However, the efficacy of X-PDT is critically dependent on the incident X-ray energy, and the selection of an optimal spectrum remains a significant clinical challenge. Motivation: A systematic approach to optimizing X-ray energy is crucial for maximizing dose enhancement and translating X-PDT’s potential into effective clinical outcomes. Aim: This study therefore aims to identify the optimal X-ray energy for X-PDT by systematically evaluating the dose enhancement provided by nanoprobes across a range of clinically relevant energies. Proposed Methodology: We developed a Geant4-based Monte Carlo model to simulate the absorbed dose in a tumor phantom, both with and without X-PDT nanoprobes, under various X-ray energies (20–160 kVp). The dose enhancement ratio (DER) was calculated to quantify the sensitization effect. To validate our model, the simulated dose data were directly correlated with in vivo experimental tumor growth inhibition (TGI) rates. Main Results: The absorbed dose peaks at shallow depths (<1.0 mm), and the 60 kVp X-ray beam yielded the highest peak dose and the maximum DER. Furthermore, the absorbed dose calculated in the model incorporating nanoprobes showed a stronger correlation with experimental TGI than the model without them, confirming the simulation’s predictive value. Conclusions: There is an optimized X-ray excitation energy value for maximizing the therapeutic effect for X-PDT. The simulation method provides a potential way to optimize the treatment protocols for X-PDT. But accurate simulation needs to be carried out in combination with more biological modeling.