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

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