Imaging and pharmacokinetics of (64)Cu-DOTA-HB22.7 administered by intravenous, intraperitoneal, or subcutaneous injection to mice bearing non-Hodgkin's lymphoma xenografts

Mol Imaging Biol. Mar-Apr 2009;11(2):79-87. doi: 10.1007/s11307-008-0148-1. Epub 2008 Oct 24.

Abstract

Purpose: The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of (64)Cu-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 (64)Cu-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of (64)Cu were performed to determine the pharmacokinetics and clearance of (64)Cu-DOTA-HB22.7.

Results: (64)Cu-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 (64)Cu-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 (64)Cu-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics*
  • Copper Radioisotopes / administration & dosage
  • Copper Radioisotopes / pharmacokinetics*
  • Female
  • Flow Cytometry
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / pharmacokinetics
  • Injections
  • Lymphoma, Non-Hodgkin / diagnostic imaging*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Succinimides / administration & dosage
  • Succinimides / pharmacokinetics
  • Tissue Distribution
  • Transplantation, Heterologous
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Copper Radioisotopes
  • DOTA-NHS
  • Immunoconjugates
  • Radiopharmaceuticals
  • Succinimides