Dosimetry of Nano-Radio-Ytterbium Therapy by MIRD and MCNP methods for humans’ organs

Abstract

Introduction: Nano radio-pharmaceutical therapy (NRPT) is a new method for solid tumor therapy. The treatment uses a radioactive form of radionuclide encapsulated in the poly amido amine dendrimers. The poly (amidoamine) (PAMAM) dendrimers have attracted attentions for cancer treatment by their characteristics of targeted drug carriers, delivery agents, and imaging agents in human systems. We have reported the preparation of dendrimer encapsulated ytterbium-175 radio- nanoparticles and its biodistribution in tumor bearing rats.175Yb (T1/2=4.2 days), decays to stable 175Lu with a β- emitter with 470 keV maximum energy (86.5%) and γ photons of 113 keV (1.9%), 282keV (3.1%) and 396 keV (6.5%) that are appropriate for imaging. This paper aims at comparing dosimetric assessments in human performed with Monte Carlo codes and MIRD based on the experimental results of biodistribution of dendrimer encapsulated ytterbium-175.Materials and Methods: All chemical materials including, Ytterbium (III) oxide (Yb2O3), PAMAMG5-NH2 dendrimer in 5% methanol solution and HNO3, Sodium boro- hydride (NaBH4) were purchased from Sigma Aldrich Chemical Co. USA and Merck, Germany. For biodistribution study 20 female Balb/c mice were purchased from Pasteur Institute of Iran. To estimate the absorbed dose by both methods, MCNP and MIRD, the cumulated activity in source organs were calculated by the percentage of injected dose in humans’ organs. The residence times (τ) in the source organs were obtained by integration of respective fit functions, on biokinetics curve, after accounting for the physical decay of the 175Yb. The dose calculation was done for a certain group of organs of human following the MIRD technique. To simulate the problem with MCNP, the ORNL phantom was used. The desired result for this study is absorbed doses of vital organs (liver, spleen, lung and kidney). Results: The maximum uptake of radio-compound are in the liver, lung and spleen. The biodistribution shows the characteristics of nanoparticles such as size and surface hydrophobicity that determine the amount of adsorbed radiopharmaceuticals in organs. The initial fast distribution of radiotracer is throughout liver, lung, and Bone, with slower accumulation in blood and spleen. The result of 2 methods (MIRD versus MCNPX) reveals that MIRD underestimate the absorbed dose for bladder, bone, lung, and ovaries while overestimate for liver, muscle and spleen. In this study the absorbed dose from 175Yb- PAMAM estimated by MCNPX for liver, lung, spleen, kidney and bone are 1.266, 8.081E-01, 8.347E-01, 3.979E-02 and 1.706E-02 mGy/MBq respectively Conclusion: Owing to the stability of PAMAM encapsulated Yb-175 and the size of nano- particle the concentrations are mostly in liver and lungs. State of- the-art dosimetry depends on the duration of the biokinetics of the radiopharmaceutical and a calculation of residence times including an analysis of the errors associated with the respective calculation that aimed in this study. The results showed that this nano-radiopharmaceutical has potential of application for liver and lung tumors.