Positron Emission Tomography of 64Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL
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This study aims to evaluate 64Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.
64Cu 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.
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.
PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.
Key words64Cu-rituximab immunoPET Radioimmuno imaging
We thank Drs. Nicholas Van Bruggen at Genentech. We also thank Drs. Fred Chin, David Dick, and the staff in the radiochemistry and cyclotron facilities, the small animal imaging center, and Canary Center at Stanford for Cancer Early Detection for instrumentation support and analysis. This work was supported in part by grants from Genentech (South San Francisco, CA) and NCI ICMIC P50-CA114747 (SSG).
Conflict of interest disclosure
The authors declare no conflict of interests.
- 7.Dearling JL, Voss SD, Dunning P, Snay E, Fahey F, Smith SV, et al (2011) Imaging cancer using PET—the effect of the bifunctional chelator on the biodistribution of a (64)Cu-labeled antibody. Nucl Med Biol 38: 29–38Google Scholar
- 13.Li J, Zheng H, Trent J, Bates P, Ng CK (2009) Evaluation of 64Cu-DOTA-AS1411 as a PET tracer for lung cancer imaging. J Nucl Med Meet (Abstracts) 50:1915Google Scholar
- 14.Li L, Bading J, Yazaki PJ, Ahuja AH, Crow D, Colcher D et al (2007) A versatile bifunctional chelate for radiolabeling humanized anti-CEA antibody with In-111 and Cu-64 at either thiol or amino groups: PET imaging Of CEA-positive tumors with whole antibodies. Bioconjugate Chem 19:89–96CrossRefGoogle Scholar
- 33.Tsukamoto N, Kojima M, Hasegawa M, Oriuchi N, Matsushima T, Yokohama A et al (2007) The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer 110:652–659PubMedCrossRefGoogle Scholar
- 34.(1996) Radiological protection and safety in medicine. Annals of the ICRP 26: 1–31Google Scholar