Purpose: Photoelectric dose enhancement using metallic biomaterials continues gaining popularity among methods of radiotherapy (RT) improvement. High-Z materials such as gold, platinum, or gadolinium are commonly attached to targeting proteins or formed into colloid nanoparticles which eject photoelectrons while under low-energy x-rays. When these biomaterials are introduced to the tumor microenvironment, typical external beam RT can deliver increased local dose by this method. Already existing FDA-approved metallic biomaterials such as specific chemotherapy drugs or MRI contrast agents could be implemented with multiple functions by providing RT dose enhancement in addition to their primary function. In this work, we estimate the potential dose enhancement provided by FDA-approved materials.
Methods: Dose enhancement estimations were determined by a Monte Carlo-simulated fluence from a 6MV clinical LINAC directed to a homogeneous metallic biomaterial distribution at 20cm depth (10cm x 10cm field) in an infinite slab tissue-equivalent phantom. Photoelectron dose was calculated corresponding to the fluence energy spectrum, concentration of metallic biomaterial, and the metallic photoelectric absorption coefficients. This was repeated for gadolinium and platinum nanoparticles; gadolinium-based contrast agents; and platinum-based chemotherapy drugs.
Results: To achieve a clinically significant dose-enhancement factor (DEF) of 1.2, the metallic biomaterial concentrations were estimated as 6mg/ml for Gd and 4.9mg/ml for Pt. Using FDA-approved intravenous delivery, this translates to 1%ID/ml of Omniscan or 0.5%ID/ml of Magnevist contrast agents; or 2%ID/ml of Carboplatin or 0.5%ID/ml of Cisplatin chemotherapy drugs. If 100%ID were to localize to the cancer site, the DEF would be 20,38,11, and 40 for Omniscan, Magnevist, Carboplatin, and Cisplatin, respectively.
Conclusion: Preliminary estimations showed that FDA-approved biomaterials could potentially deliver clinically significant DEF at reasonably achievable concentrations. In future work, we seek to investigate local delivery or protein-targeting of these biomaterials to improve localization and increase the DEF.