Positron emission tomography of 64Cu-DOTA-Rituximab in a transgenic mouse model expressing human CD20 for clinical translation to image NHL.
OBJECTIVE
This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.


METHODS
(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n = 3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n = 6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n = 6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.


RESULTS
PETRIT was obtained with a specific activity of 545 ± 38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean ± STD) with and without pre-dose was 1.76 ± 0.43% and 16.5 ± 0.45%, respectively (P value = 0.01). Liver uptake with and without pre-dose was 0.41 ± 0.51% and 0.52 ± 0.17% (P value = 0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8 ± 0.4 μSv/MBq and the spleen at 99 ± 4 μSv/MBq, respectively.


CONCLUSIONS
PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.
Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305, USA. anatarajan@stanford.edu
Arutselvan
A
Natarajan
Gayatri
G
Gowrishankar
Carsten H
CH
Nielsen
Sen
S
Wang
Andrei
A
Iagaru
Michael L
ML
Goris
Sanjiv Sam
SS
Gambhir
D000328:Adult; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003301:Copper Radioisotopes; D004307:Dose-Response Relationship, Radiation; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007553:Isotope Labeling; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D014057:Tomography, X-Ray Computed; D057170:Translational Research, Biomedical
C578180:64Cu-DOTA-rituximab; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid