IFEG   20353
INSTITUTO DE FISICA ENRIQUE GAVIOLA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
177Lu-Anti-CD20 monoclonal antibody: Labeling and biologic evaluation
Autor/es:
E. RIVA; P. AUDICIO; M. TASSANO; M. FERNÁNDEZ; G. CASTELLANO; P. CABRAL; P. OLIVER; H. BALTER
Lugar:
Lugano
Reunión:
Simposio; Educational Cancer Convention Lugano; 2010
Institución organizadora:
European School of Oncology
Resumen:
Anti-CD20 monoclonal antibody (Mab) is used for the treatment of CD20+ NHL. Its labeling with ß-emitters increases therapeutic effectiveness. Lutetium 177 is a ß- and g-emitter whose properties allow the analysis of in vivo biodistribution. Mab (Mabthera®) was conjugated with 3 mmol of DOTA-Ossu and incubated 18 hours at 4ºC, then purified by G-25. Conjugated DOTA-Mab were stored at 4 and −20ºC for stability evaluation. Labeling was performed by addition of 7 mCi of 177 Lu and 1 mg of gentisic acid to 500 mg of Mab-DOTA, incubated 30 min at 37ºC and purified by G25. Stability of 177Lu-Mab in human and saline serum was analyzed by 2 chromatographic systems: ITLC-SG and ITLC- SG strips (BSA 5%) with EtOH-NH4OH-H2O (2:1:5) and Sodium acetate 14% as mobile phase, respectively. Biodistribution studies were carried out in normal mice (n=3) at 4, 16 and 24 hours post injection of 1.1 mCi of Mab-DOTA-177Lu. Immunoafinity was tested in leucocyte membranes extracts. Biodistribution studies were done at same conditions using 150 mg/m² and 250 mg/m² of unlabelled Mab. Dosimetric studies were done by Monte Carlo Simulation. Labeling yields of 75% and radiochemical purity (Rqp) >97% after purification for up to 24 hours, both in human and saline serum. Rqp and stability of labeled Mab at 4ºC and −20ºC showed no differencies. Immunoafinity assays confirmed that its activity against CD20 was not affected. Biodistribution of cold Mab showed hepatic uptake (40%) and urinary elimination (30%) at 24 hours. Studies with cold Mab showed significant decrease in the uptake of 177Lu-Mab by blood cells and liver tissue. At theoric dosimetric studies, 83% of the total administered dose was deposited in the tumor mass. This methodology is suitable for the labeling of 177Lu-Mab giving reliable results that make it adequate as a therapeutic radiopharmaceutical.