Nonclinical Pharmacodynamics of Boron Neutron Capture Therapy Using Direct Intratumoral Administration of a Folate Receptor Targeting Novel Boron Carrier

Background Boron neutron capture therapy (BNCT) is a precise particle radiation therapy known for its unique cellular targeting ability. The development of innovative boron carriers is crucial for the advancement of BNCT technologies. Our previous study demonstrated the potential of PBC-IP administered via convection-enhanced delivery (CED) in an F98 rat glioma model. This approach significantly extended rat survival in neutron irradiation experiments, with half achieving long-term survival, akin to a cure, in a rat brain tumor model. Our commitment to clinical applicability has spurred additional nonclinical pharmacodynamic research, including an investigation into the effects of cannula position and the time elapsed post-CED administration.Methods In comprehensive in vivo experiments conducted on an F98 rat brain tumor model, we meticulously examined the boron distribution and neutron irradiation experiments at various sites and multiple time intervals following CED administration.Results The PBC-IP showed substantial efficacy for BNCT, revealing minimal differences in tumor boron concentration between central and peripheral CED administration, although a gradual decline in intratumoral boron concentration post-administration was observed. Therapeutic efficacy remained robust, particularly when employing cannula insertion at the tumor margin, compared to central injections. Even delayed neutron irradiation showed notable effectiveness, albeit with a slightly reduced survival period. These findings underscore the robust clinical potential of CED-administered PBC-IP in the treatment of malignant gliomas, offering adaptability across an array of treatment protocols.Conclusions This study represents a significant leap forward in the quest to enhance BNCT for the management of malignant gliomas, opening promising avenues for clinical translation. Boron neutron capture therapy (BNCT) is a treatment that uses targeted neutron radiation to kill cancer cells that have absorbed a boron compound. PBC-IP is a new drug that carries boron and it can be delivered directly into brain tumors through a method called convection-enhanced delivery (CED). Prior research has shown that direct delivery of PBC-IP using CED followed by targeted radiation increased the survival of rats with brain tumors. The authors of this study looked to see if where they delivered the PBC-IP and when they gave neutron radiation made a difference in how well the treatment worked. To do this they treated rats with brain tumors by delivering PBC-IP in the middle or edge of the tumor and then gave neutron radiation at different time points. Their results show treatment with delivery of PBC-IP to the center or the edge of the tumor, and radiation for up to 24 hours after delivery of PBC-IP were all similarly effective.