INVESTIGADORES
CASTELLANO Gustavo Eugenio
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.