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

  • Shiloh M. Martin
  • Robert T. O’Donnell
  • David L. Kukis
  • Craig K. Abbey
  • Hayes McKnight
  • Julie L. Sutcliffe
  • Joseph M. Tuscano
Research Article

DOI: 10.1007/s11307-008-0148-1

Cite this article as:
Martin, S.M., O’Donnell, R.T., Kukis, D.L. et al. Mol Imaging Biol (2009) 11: 79. doi:10.1007/s11307-008-0148-1

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.

Key words

HB22.7 CD22 Non-Hodgkin’s lymphoma PET 64Cu 

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

Copyright information

© Academy of Molecular Imaging 2008

Authors and Affiliations

  • Shiloh M. Martin
    • 1
  • Robert T. O’Donnell
    • 1
    • 2
  • David L. Kukis
    • 3
  • Craig K. Abbey
    • 4
  • Hayes McKnight
    • 1
  • Julie L. Sutcliffe
    • 3
    • 5
  • Joseph M. Tuscano
    • 1
    • 2
    • 6
  1. 1.Division of Hematology and Oncology, Department of Internal MedicineUniversity of California, Davis Cancer CenterDavisUSA
  2. 2.Northern California Veterans Administration Healthcare SystemSacramentoUSA
  3. 3.Center for Molecular and Genomic ImagingUniversity of California DavisDavisUSA
  4. 4.Department of PsychologyUniversity of California Santa BarbaraSanta BarbaraUSA
  5. 5.Department of Biomedical EngineeringUniversity of California DavisDavisUSA
  6. 6.Department of Internal Medicine, Division of Hematology and OncologySacramentoUSA