PET/SPECT/Spectral‐CT/CBCT imaging in a small‐animal radiation therapy platform: A Monte Carlo study—Part II: Biologically guided radiotherapy.

Background: This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small‐animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small‐animal models of cancer and the translation of preclinical RT studies into clinical practices. Purpose: The main aim was to explore the feasibility of biologically guided RT implemented within a small‐animal radiation therapy (SART) platform, with integrated quad‐modal on‐board positron emission tomography (PET), single‐photon emission computed tomography, photon‐counting spectral CT, and cone‐beam CT (CBCT) imaging, in a Monte Carlo model as a proof‐of‐concept. Methods: We developed a SART workflow employing quad‐modal imaging guidance, integrating multimodal image‐guided RT and emission‐guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real‐time adjustments to radiation treatment beams for precise targeting in the presence of a 2‐mm setup error. Molecular image‐guided RT, incorporating a dose escalation/de‐escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT‐delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F‐PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy‐related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01–0.02. Results: EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2‐mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image‐guided RT. In the dose‐painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ‐at‐risk (OAR) dose comparable to the low‐dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy‐related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. Conclusions: The results demonstrated the successful implementation of biologically guided RT within the proposed quad‐model image‐guided SART platform, with potential applications in preclinical RT and adaptive RT studies. [ABSTRACT FROM AUTHOR]