Dosimetric Studies of Anti-CD20 Labeled With Therapeutic Radionuclides at IPEN/CNEN-SP

Abstract

Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/betaradionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving thenormal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is basedon information obtained in dosimetric studies. Beta emitting radionuclides such as 131I, 188Re, 90Y, 177Luand 166Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) isa chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkinlymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeuticefficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDAapproval for NHL treatment: 131I-AntiCD20 (Bexar®) and 90Y-AntiCD20 (Zevalin®). Techniques for theradiolabeling of 188Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluatethe clinical use of this radionuclide in particular. The use of 188Re (T1/2 17h) produced by the decay of188W (T1/2 69d), from an 188W/188Re generator system, has represented an alternative to RIT. Beyond highenergy beta emission for therapy, 188Re also emits gamma rays (155keV) suitable for image. The aim ofthis new project is to compare the labeling of anti-CD20 with 188Re with the same MAb labeled with 131I,177Lu, 90Y and even 99mTc. The first step in this project is the review of the published data availableconcerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN,taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities andbiodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platformthrough VB.NET and C++ for biodistribution and dosimetric studies of 188Re-AntiCD20 in mice,simulating other compartmental systems and radiopharmaceuticals. After the model definition, asimulation will be performed using the 188Re-AntiCD20, evaluating tumor uptake, critical organsdosimetry and biodistribution study. The total beta radiation dose received by the bone marrow will alsobe evaluated for all radiopharmaceuticals.