Positron Emission Tomography of (64)Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL
Research output: Contribution to journal › Journal article › Research › peer-review
PURPOSE: This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation. PROCEDURES: (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.
Original language | English |
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Journal | Molecular Imaging and Biology |
Volume | 14 |
Issue number | 5 |
Pages (from-to) | 608-616 |
Number of pages | 9 |
ISSN | 1536-1632 |
DOIs | |
Publication status | Published - 2012 |
ID: 37561491