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Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin’s Lymphoma Xenografts

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Abstract

Purpose

The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of 64Cu-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP), and subcutaneously (SQ).

Procedures

Mice bearing human non-Hodgkin’s lymphoma (NHL) xenografts were injected IV, IP, or SQ with 64Cu-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of 64Cu were performed to determine the pharmacokinetics and clearance of 64Cu-DOTA-HB22.7.

Results

64Cu-DOTA-HB22.7 demonstrated equivalent tumor targeting within 24–48 h, regardless of the route of administration. Organ biodistribution confirmed tumor-specific targeting. Blood pharmacokinetics demonstrated that 64Cu-DOTA-HB22.7 accessed the bloodstream after IP and SQ administration to a similar degree as IV administration, albeit at a slower rate.

Conclusions

These findings establish 64Cu-DOTA-HB22.7 as a potential radioimmunotherapeutic and/or NHL-specific imaging agent. These findings provide evidence that IP and SQ administration can achieve results equivalent to IV administration and may lead to more efficient, reproducible treatment plans for antibody-based therapeutics.

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Abbreviations

64Cu:

Copper-64

DOTA-NHS-ester:

1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid mono(N-hydroxysuccinimidyl ester)

Ig:

immunoglobulin

IV:

intravenous

IP:

intraperitoneal

mAb:

monoclonal antibody

NHL:

non-Hodgkin’s lymphoma

RIT:

radioimmunotherapy

SQ:

subcutaneous

TLC:

thin layer chromatography

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Acknowledgements

The authors would like to thank the CMGI staff, particularly Jennifer Fung and Chris Griesemer, for their support and expertise in small animal imaging. The authors would also like to thank Yunpeng Ma for assistance with organ harvesting for biodistribution studies. The production of Cu-64 at Washington University School of Medicine is supported by the NCI grant R24 CA86307. This work was supported by R33 CA89706 (NIH, NCI); 00-00764V-0133, the University of California Cancer Research Program, VA Merit grants, 1337754 and 7855423, Small Animal Resource Program Grant R24 CA110804 Leukemia and Lymphoma Society Translational Research Award, Schwedler Foundation and the deLeuze Endowment for the non-toxic cure of lymphoma.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis Cancer Center, Davis, CA, USA

    Shiloh M. Martin, Robert T. O’Donnell, Hayes McKnight & Joseph M. Tuscano

  2. Northern California Veterans Administration Healthcare System, Sacramento, CA, USA

    Robert T. O’Donnell & Joseph M. Tuscano

  3. Center for Molecular and Genomic Imaging, University of California Davis, Davis, CA, USA

    David L. Kukis & Julie L. Sutcliffe

  4. Department of Psychology, University of California Santa Barbara, Santa Barbara, CA, USA

    Craig K. Abbey

  5. Department of Biomedical Engineering, University of California Davis, Davis, CA, USA

    Julie L. Sutcliffe

  6. Department of Internal Medicine, Division of Hematology and Oncology, 4501 X street, Suite 3016, Sacramento, CA, 95630, USA

    Joseph M. Tuscano

Authors
  1. Shiloh M. Martin
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  2. Robert T. O’Donnell
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  3. David L. Kukis
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  4. Craig K. Abbey
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  5. Hayes McKnight
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  6. Julie L. Sutcliffe
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  7. Joseph M. Tuscano
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Corresponding author

Correspondence to Joseph M. Tuscano.

Additional information

Julie L. Sutcliffe and Joseph M. Tuscano—these authors jointly supervised this study.

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Martin, S.M., O’Donnell, R.T., Kukis, D.L. et al. Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin’s Lymphoma Xenografts. Mol Imaging Biol 11, 79–87 (2009). https://doi.org/10.1007/s11307-008-0148-1

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  • DOI: https://doi.org/10.1007/s11307-008-0148-1

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