Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma

The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorpo...

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Bibliographic Details
Published inCurrent radiopharmaceuticals Vol. 9; no. 1; p. 54
Main Authors Massicano, Adriana V F, Pujatti, Priscilla B, Alcarde, Lais F, Suzuki, Miriam F, Spencer, Patrick J, Araújo, Elaine B
Format Journal Article
LanguageEnglish
Published United Arab Emirates 2016
Subjects
Animals
Drug Stability
Humans
Lutetium - administration & dosage
Lutetium - chemistry
Lutetium - pharmacokinetics
Lymphoma, Non-Hodgkin - radiotherapy
Mice
Mice, SCID
Radiopharmaceuticals - administration & dosage
Radiopharmaceuticals - chemistry
Radiopharmaceuticals - pharmacokinetics
Rituximab - administration & dosage
Rituximab - chemistry
Rituximab - pharmacokinetics
Succinimides - chemistry
Tissue Distribution
Xenograft Model Antitumor Assays
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Summary:The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.
ISSN:1874-4729