COMPARATIVE PHARMACOKINETICS, BIODISTRIBUTION AND DOSIMETRY OF 212Pb (ALPHA-EMITTER) LABELED ANTIBODY VS PEPTIDE VS SMALL MOLECULE

With the advent of newly and more reliably designed targeted therapy methods in the past several years, targeted radionuclide therapy has attracted more attentions around the world as a more reliable treatment modality in combination with other well established traditional cancer treatments i.e., external beam radiotherapy and chemotherapy. Alpha particles have a high relative biological effectiveness (RBE) due to their high linear energy transfer (LET). However, to utilize them for therapeutic purposes, precise human body dosimetry calculation is required. The measurement of their uptake and biodistribution can be quite challenging. Also, due to the complex biology of different types of cells, their shapes and functions, there is not a simple and clear understanding of the mechanism of action that fits all. This study aims to estimate and compare the human organ dosimetry of the alpha emitter, 212Pb, from animal data assuming that it is conjugated with three different types of commonly used targeting nanoparticles. For this purpose, the pre-published animal data of three different radionuclide labeled peptide, antibody, and small molecule carriers were selected and converted to human data. Then a compartmental model was designed for each of them to fit the model to the human data with 212Pb, half-life of 10.64 hours. Once each model reached the desired fit, the area under the curves were extracted then the estimated human organ dosimetry calculations took place via the MIRD scheme. The organ dosimetry results for 212Pb + three different carriers are presented in Tables 14, 17, and 20.