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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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Abstract

Purpose

This study aims to evaluate 64Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.

Procedures

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.

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Molecular Imaging Program at Stanford, Stanford University, Stanford, CA, 94305, USA

    Arutselvan Natarajan, Gayatri Gowrishankar, Carsten H. Nielsen, Sen Wang & Andrei Iagaru

  2. Division of Nuclear Medicine, Department of Radiology, Stanford University, Stanford, CA, 94305, USA

    Michael L. Goris & Sanjiv Sam Gambhir

  3. Department of Bioengineering, Department of Materials Science and Engineering, Bio-X Program, Stanford University, Stanford, CA, 94305, USA

    Sanjiv Sam Gambhir

  4. Department of Radiology, Stanford University, James H Clark Center E150, 318 Campus Drive, Stanford, CA, 94305-5427, USA

    Sanjiv Sam Gambhir

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  1. Arutselvan Natarajan
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Correspondence to Sanjiv Sam Gambhir.

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Natarajan, A., Gowrishankar, G., Nielsen, C.H. et al. Positron Emission Tomography of 64Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL. Mol Imaging Biol 14, 608–616 (2012). https://doi.org/10.1007/s11307-011-0537-8

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