RT Journal Article
SR Electronic
T1 Cure of Micrometastatic B-Cell Lymphoma in a SCID Mouse Model Using <sup>213</sup>Bi-Anti-CD20 Monoclonal Antibody
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 109
OP 116
DO 10.2967/jnumed.122.263962
VO 64
IS 1
A1 Havlena, Gregory T.
A1 Kapadia, Nirav S.
A1 Huang, Peng
A1 Song, Hong
A1 Engles, James
A1 Brechbiel, Martin
A1 Sgouros, George
A1 Wahl, Richard L.
YR 2023
UL http://jnm.snmjournals.org/content/64/1/109.abstract
AB We studied the feasibility of using the α-emitting 213Bi-anti-CD20 therapy with direct bioluminescent tracking of micrometastatic human B-cell lymphoma in a SCID mouse model. Methods: A highly lethal SCID mouse model of minimal-tumor-burden disseminated non-Hodgkin lymphoma (NHL) was established using human Raji lymphoma cells transfected to express the luciferase reporter. In vitro and in vivo radioimmunotherapy experiments were conducted. Single- and multiple-dose regimens were explored, and results with 213Bi-rituximab were compared with various controls, including no treatment, free 213Bi radiometal, unlabeled rituximab, and 213Bi-labeled anti-HER2/neu (non–CD20-specific antibody). 213Bi-rituximab was also compared in vivo with the low-energy β-emitter 131I-tositumomab and the high-energy β-emitter 90Y-rituximab. Results: In vitro studies showed dose-dependent target-specific killing of lymphoma cells with 213Bi-rituximab. Multiple in vivo studies showed significant and specific tumor growth delays with 213Bi-rituximab versus free 213Bi, 213Bi-labeled control antibody, or unlabeled rituximab. Redosing of 213Bi-rituximab was more effective than single dosing. With a single dose of therapy given 4 d after intravenous tumor inoculation, disease in all untreated controls, and in all mice in the 925-kBq 90Y-rituximab group, progressed. With 3,700 kBq of 213Bi-rituximab, 75% of the mice survived and all but 1 survivor was cured. With 2,035 kBq of 131I-tositumomab, 75% of the mice were tumor-free by bioluminescent imaging and 62.5% survived. Conclusion: Cure of micrometastatic NHL is achieved in most animals treated 4 d after intravenous tumor inoculation using either 213Bi-rituximab or 131I-tositumomab, in contrast to the lack of cures with unlabeled rituximab or 90Y-rituximab or if there was a high tumor burden before radioimmunotherapy. α-emitter–labeled anti-CD20 antibodies are promising therapeutics for NHL, although a longer-lived α-emitter may be of greater efficacy.